U.S. patent number 10,308,650 [Application Number 15/534,734] was granted by the patent office on 2019-06-04 for pesticidally active tetracyclic derivatives with sulfur containing substituents.
This patent grant is currently assigned to SYNGENTA PARTICIPATIONS AG. The grantee listed for this patent is Syngenta Participations AG. Invention is credited to Jerome Yves Cassayre, Andrew Edmunds, Roger Graham Hall, Ottmar Franz Hueter, Andre Jeanguenat, Pierre Joseph Marcel Jung, Michel Muehlebach.
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United States Patent |
10,308,650 |
Jung , et al. |
June 4, 2019 |
Pesticidally active tetracyclic derivatives with sulfur containing
substituents
Abstract
Compounds of formula (I) wherein the substituents are as defined
in claim 1, and the agrochemically acceptable salts, stereoisomers,
enantiomers, tautomers and N-oxides of those compounds, can be used
as insecticides and can be prepared in a manner known per se.
##STR00001##
Inventors: |
Jung; Pierre Joseph Marcel
(Stein, CH), Hueter; Ottmar Franz (Stein,
CH), Edmunds; Andrew (Stein, CH),
Muehlebach; Michel (Stein, CH), Cassayre; Jerome
Yves (Stein, CH), Hall; Roger Graham (Stein,
CH), Jeanguenat; Andre (Stein, CH) |
Applicant: |
Name |
City |
State |
Country |
Type |
Syngenta Participations AG |
Basel |
N/A |
CH |
|
|
Assignee: |
SYNGENTA PARTICIPATIONS AG
(Basel, CH)
|
Family
ID: |
54780333 |
Appl.
No.: |
15/534,734 |
Filed: |
December 4, 2015 |
PCT
Filed: |
December 04, 2015 |
PCT No.: |
PCT/EP2015/078609 |
371(c)(1),(2),(4) Date: |
June 09, 2017 |
PCT
Pub. No.: |
WO2016/091731 |
PCT
Pub. Date: |
June 16, 2016 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20170349581 A1 |
Dec 7, 2017 |
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Foreign Application Priority Data
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Dec 11, 2014 [EP] |
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14197275 |
Jul 30, 2015 [EP] |
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15179050 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C07D
471/04 (20130101); A01N 43/90 (20130101); C07D
491/048 (20130101) |
Current International
Class: |
A01N
43/90 (20060101); C07D 471/04 (20060101); C07D
491/048 (20060101) |
Foreign Patent Documents
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3225386 |
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Jan 1984 |
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DE |
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3445299 |
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Jun 1986 |
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DE |
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6323087 |
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May 2018 |
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JP |
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2012086848 |
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Jun 2012 |
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WO |
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Other References
Extended European Search Report for 14197275.2 dated Mar. 30, 2015.
cited by applicant .
International Search Report and Written Opinion for
PCT/EP2015/078609, dated Mar. 16, 2016. cited by applicant.
|
Primary Examiner: Pryor; Alton N
Attorney, Agent or Firm: Herbert; Toni-Junell Dinsmore Shohl
LLP
Claims
The invention claimed is:
1. A compound of formula I, ##STR00187## wherein A is CH or N; X is
S, SO or SO.sub.2; R.sub.1 is C.sub.1-C.sub.4alkyl,
C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.4haloalkyl,
C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl; or is
C.sub.3-C.sub.6cycloalkyl mono- or polysubstituted by substituents
selected from the group consisting of halogen, cyano,
C.sub.1-C.sub.4haloalkyl and C.sub.1-C.sub.4alkyl; or is
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl mono- or
polysubstituted by substituents selected from the group consisting
of halogen, cyano, C.sub.1-C.sub.4haloalkyl and
C.sub.1-C.sub.4alkyl; R.sub.2 is hydrogen, halogen,
C.sub.1-C.sub.4haloalkylsulfanyl, C.sub.1-C.sub.4haloalkylsulfinyl,
C.sub.1-C.sub.4haloalkylsulfonyl, O(C.sub.1-C.sub.4haloalkyl),
--SF.sub.5, --C(O)C.sub.1-C.sub.4haloalkyl, cyano,
C.sub.1-C.sub.6haloalkyl or is C.sub.1-C.sub.6haloalkyl substituted
by one or two substituents selected from the group consisting of
hydroxyl, methoxy and cyano; or is C.sub.3-C.sub.6cycloalkyl which
can be mono- or polysubstituted by substituents selected from the
group consisting of halogen, cyano, C.sub.1-C.sub.4haloalkyl and
C.sub.1-C.sub.4alkyl; G.sub.1 is N or CR.sub.4; G.sub.2 is N or
CR.sub.5; G.sub.3 is O, S or NR.sub.6; R.sub.6 is
C.sub.1-C.sub.4alkyl which can be mono- or polysubstituted by
substituents selected from the group consisting of halogen and
C.sub.1-C.sub.2alkylsulfinyl; R.sub.4 and R.sub.5, independently
from each other, are hydrogen, halogen, cyano, nitro,
C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, or are
C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by
R.sub.8; or are C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl
which can be mono- or polysubstituted by R.sub.9; or R.sub.4 and
R.sub.5, independently from each other, are C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.1-C.sub.6haloalkoxy,
C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6alkylsulfanyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.6alkylsulfinyl
C.sub.1-C.sub.6haloalkylsulfanyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.6haloalkylsulfinyl or hydroxyl; R.sub.8 and R.sub.9,
independently from each other, are halogen, nitro, cyano,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkoxy,
C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4haloalkyl; L.sub.1, L.sub.2,
L.sub.3 and L.sub.4 form together with the two carbon atoms to
which L.sub.1 and L.sub.4 are attached, an aromatic or partially
saturated carbocyclic or heterocyclic ring system; wherein L.sub.1
is nitrogen, S(O)n, oxygen, N--R.sub.10a or C(R.sub.10a).sub.m;
L.sub.2 is nitrogen, S(O)n, oxygen, N--R.sub.10b or
C(R.sub.10b).sub.m; L.sub.3 is nitrogen, S(O)n, oxygen,
N--R.sub.10c, or C(R.sub.10c).sub.m; L.sub.4 is nitrogen, S(O)n,
oxygen, a direct bond, N--R.sub.10d or C(R.sub.10d).sub.m; with the
provisos that no more than 2 substituents selected from L.sub.1,
L.sub.2, L.sub.3 and L.sub.4 can be oxygen or sulfur; and if two L
groups are oxygen, they are not adjacent to each other; and no more
than three L groups can be nitrogen; n is 0 to 2; m is 1 or 2;
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, amino, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.4alkoxy C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio,
C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl,
C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl,
C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.2-C.sub.6alkylcarbonyl,
C.sub.2-C.sub.6alkoxycarbonyl, C.sub.2-C.sub.6 haloalkylcarbonyl,
C.sub.2-C.sub.6haloalkoxycarbonyl, (C.sub.1-C.sub.6alkyl)NH,
(C.sub.1-C.sub.6 alkyl).sub.2N, (C.sub.1-C.sub.6 cycloalkyl)NH,
(C.sub.1-C.sub.6cycloalkyl).sub.2N,
C.sub.1-C.sub.6alkylcarbonylamino,
C.sub.1-C.sub.6cycloalkylcarbonylamino or --SF.sub.5; additionally
one of R.sub.10a, R.sub.10b, R.sub.10c and R.sub.10d can be oxo; or
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are C.sub.3-C.sub.6cycloalkyl mono- or polysubstituted
by substituents selected from the group consisting of
C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkyl and cyano; or
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are phenyl which can be mono- or polysubstituted by
substituents selected from the group consisting of halogen,
C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4alkoxy and cyano; and agrochemically acceptable
salts, stereoisomers, enantiomers, tautomers and N-oxides of those
compounds.
2. The compound of claim 1, represented by the compounds of formula
I-1 ##STR00188## wherein the substituents X, A, R.sub.1, R.sub.2,
R.sub.6, G.sub.3, L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as
defined under formula I in claim 1.
3. The compound of claim 1, represented by the compounds of formula
I-2 ##STR00189## wherein the substituents X, A, R.sub.1, R.sub.2,
R.sub.6, G.sub.3, L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as
defined under formula I in claim 1.
4. The compound of claim 1, represented by the compounds of formula
I-3 ##STR00190## wherein the substituents X, A, R.sub.1, R.sub.2,
R.sub.6, G.sub.3, L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as
defined under formula I in claim 1.
5. The compound of claim 1, represented by the compounds of formula
I-4 ##STR00191## wherein the substituents X, A, R.sub.1, R.sub.2,
R.sub.6, G.sub.3, L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as
defined under formula I in claim 1.
6. The compound of claim 1, represented by the compounds of formula
I-5a ##STR00192## wherein G.sub.1 is N or CH; G.sub.2 is N or CH;
R.sub.2 is C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4halosulfanyl or
C.sub.1-C.sub.4halosulfinyl; A is N or CH; R.sub.6 is
C.sub.1-C.sub.4alkyl; X is S or SO.sub.2; R.sub.1 is
C.sub.1-C.sub.4alkyl; and Ja is selected from the group consisting
of ##STR00193## wherein R.sub.10a, R.sub.10b, R.sub.10c, and
R.sub.10d, independently from each other, are selected from the
group consisting of hydrogen, halogen, cyano, cyclopropyl,
C.sub.1-C.sub.4 alkyl and C.sub.1-C.sub.4haloalkyl.
7. A pesticidal composition, which comprises at least one compound
of formula I according to claim 1 or a tautomer thereof, in each
case in free form or in agrochemically utilizable salt form, as
active ingredient and at least one auxiliary.
8. A method for controlling pests, which comprises applying the
composition according to claim 7 to the pests or their environment
with the exception of a method for treatment of the human or animal
body by surgery or therapy and diagnostic methods practised on the
human or animal body.
9. A method for protection of plant propagation material from the
attack by pests, which comprises treating the propagation material
or the site, where the propagation material is planted, with a
composition according to claim 7.
10. The plant propagation material treated in accordance with the
method described in claim 9.
Description
RELATED APPLICATION INFORMATION
This application is a 371 of International Application No.
PCT/EP2015/078609, filed 4 Dec. 2015, which claims priority to EP
14197275.2, filed 11 Dec. 2014, and EP 15179050.8, filed 30 Jul.
2015, the contents of which are incorporated herein by reference
herein.
The present invention relates to pesticidally active, in particular
insecticidally active tetracyclic derivatives containing sulfur
substituents, to compositions comprising those compounds, and to
their use for controlling animal pests (including arthropods and in
particular insects or representatives of the order Acarina).
Heterocyclic compounds with pesticidal action are known and
described, for example, in WO 2012/086848 and WO 2013/018928.
There have now been found novel pesticidally active tetracyclic
derivatives with a sulfur containing bicyclic moiety.
The present invention accordingly relates to compounds of formula
I,
##STR00002##
wherein
A represents CH or N;
X is S, SO or SO.sub.2;
R.sub.1 is C.sub.1-C.sub.4alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl,
C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl; or is
C.sub.3-C.sub.6cycloalkyl mono- or polysubstituted by substituents
selected from the group consisting of halogen, cyano,
C.sub.1-C.sub.4haloalkyl and C.sub.1-C.sub.4alkyl; or is
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl mono- or
polysubstituted by substituents selected from the group consisting
of halogen, cyano, C.sub.1-C.sub.4 haloalkyl and
C.sub.1-C.sub.4alkyl;
R.sub.2 is hydrogen, halogen, C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
O(C.sub.1-C.sub.4haloalkyl), --SF.sub.5,
--C(O)C.sub.1-C.sub.4haloalkyl, cyano, C.sub.1-C.sub.6haloalkyl or
is C.sub.1-C.sub.6haloalkyl substituted by one or two substituents
selected from the group consisting of hydroxyl, methoxy and cyano;
or is C.sub.3-C.sub.6cycloalkyl which can be mono- or
polysubstituted by substituents selected from the group consisting
of halogen, cyano, C.sub.1-C.sub.4haloalkyl and
C.sub.1-C.sub.4alkyl;
G.sub.1 is N or CR.sub.4;
G.sub.2 is N or CR.sub.5;
G.sub.3 is O, S or NR.sub.6;
R.sub.6 is C.sub.1-C.sub.4alkyl which can be mono- or
polysubstituted by substituents selected from the group consisting
of halogen and C.sub.1-C.sub.2alkylsulfinyl;
R.sub.4 and R.sub.5, independently from each other, are hydrogen,
halogen, cyano, nitro, C.sub.1-C.sub.6alkyl,
C.sub.1-C.sub.6haloalkyl, or are C.sub.3-C.sub.6cycloalkyl which
can be mono- or polysubstituted by R.sub.8; or are
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl which can be mono-
or polysubstituted by R.sub.9; or
R.sub.4 and R.sub.5, independently from each other, are
C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl,
C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkoxy,
C.sub.1-C.sub.6alkylsulfanyl, C.sub.1-C.sub.4alkylsulfonyl,
C.sub.1-C.sub.6alkylsulfinyl C.sub.1-C.sub.6haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfonyl, C.sub.1-C.sub.6haloalkylsulfinyl
or hydroxyl;
R.sub.8 and R.sub.9, independently from each other, are halogen,
nitro, cyano, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkoxy,
C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4haloalkyl;
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 form together with the two
carbon atoms to which L.sub.1 and L.sub.4 are attached, an
aromatic, partially saturated carbocyclic or heterocyclic ring
system; wherein
L.sub.1 is nitrogen, S(O)n, oxygen. N--R.sub.10a or
C(R.sub.10a).sub.m;
L.sub.2 is nitrogen, S(O)n, oxygen. N--R.sub.10b or
C(R.sub.10b).sub.m;
L.sub.3 is nitrogen, S(O)n, oxygen. N--R.sub.10c, or
C(R.sub.10c).sub.m;
L.sub.4 is nitrogen, S(O)n, oxygen, a direct bond, N--R.sub.10d or
C(R.sub.10d).sub.m; with the provisos that no more than 2
substituents selected from L.sub.1, L.sub.2, L.sub.3 and L.sub.4
can be oxygen or sulfur; and if two L groups are oxygen, they are
not adjacent to each other; and no more than three L groups can be
nitrogen;
n is 0 to 2;
m is 1 or 2;
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, amino, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.4alkoxy C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylthio,
C.sub.1-C.sub.6alkylsulfinyl, C.sub.1-C.sub.6alkylsulfonyl,
C.sub.1-C.sub.6haloalkylthio, C.sub.1-C.sub.6haloalkylsulfinyl,
C.sub.1-C.sub.6haloalkylsulfonyl, C.sub.2-C.sub.6alkylcarbonyl,
C.sub.2-C.sub.6alkoxycarbonyl, C.sub.2-C.sub.6 haloalkylcarbonyl,
C.sub.2-C.sub.6haloalkoxycarbonyl, (C.sub.1-C.sub.6alkyl)NH,
(C.sub.1-C.sub.6alkyl).sub.2N, (C.sub.1-C.sub.6cycloalkyl)NH,
(C.sub.1-C.sub.6cycloalkyl).sub.2N,
C.sub.1-C.sub.6alkylcarbonylamino,
C.sub.1-C.sub.6cycloalkylcarbonylamino or --SF.sub.5; additionally
one of R.sub.10a, R.sub.10b, R.sub.10c and R.sub.10d can be oxo;
or
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are C.sub.3-C.sub.6cycloalkyl mono- or polysubstituted
by substituents selected from the group consisting of
C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4alkyl and cyano; or
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are phenyl which can be mono- or polysubstituted by
substituents selected from the group consisting of halogen,
C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.4alkyl,
C.sub.1-C.sub.4alkoxy and cyano; and agrochemically acceptable
salts, stereoisomers, enantiomers, tautomers and N-oxides of those
compounds.
Compounds of formula I which have at least one basic centre can
form, for example, acid addition salts, for example with strong
inorganic acids such as mineral acids, for example perchloric acid,
sulfuric acid, nitric acid, a phosphorus acid or a hydrohalic acid,
with strong organic carboxylic acids, such as
C.sub.1-C.sub.4alkanecarboxylic acids which are unsubstituted or
substituted, for example by halogen, for example acetic acid, such
as saturated or unsaturated dicarboxylic acids, for example oxalic
acid, malonic acid, succinic acid, maleic acid, fumaric acid or
phthalic acid, such as hydroxycarboxylic acids, for example
ascorbic acid, lactic acid, malic acid, tartaric acid or citric
acid, or such as benzoic acid, or with organic sulfonic acids, such
as C.sub.1-C.sub.4alkane- or arylsulfonic acids which are
unsubstituted or substituted, for example by halogen, for example
methane- or p-toluenesulfonic acid. Compounds of formula I which
have at least one acidic group can form, for example, salts with
bases, for example mineral salts such as alkali metal or alkaline
earth metal salts, for example sodium, potassium or magnesium
salts, or salts with ammonia or an organic amine, such as
morpholine, piperidine, pyrrolidine, a mono-, di- or
tri-lower-alkylamine, for example ethyl-, diethyl-, triethyl- or
dimethylpropylamine, or a mono-, di- or
trihydroxy-lower-alkylamine, for example mono-, di- or
triethanolamine.
m is 1 or 2 depending on the hybridization of the carbon atom.
If m is 2 in the definition C(R.sub.10a).sub.m, R.sub.10a can be
the same or different; for example one R.sub.10a can be hydrogen
and the other methyl. This is also valid for the definitions of
C(R.sub.10b).sub.m, C(R.sub.10c).sub.m and C(R.sub.10d).sub.m.
The alkyl groups occurring in the definitions of the substituents
can be straight-chain or branched and are, for example, methyl,
ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, iso-butyl,
tert-butyl, pentyl, hexyl, nonyl, decyl and their branched isomers.
Alkylsulfanyl, alkylsulfinyl, alkylsulfonyl, alkoxy, alkenyl and
alkynyl radicals are derived from the alkyl radicals mentioned. The
alkenyl and alkynyl groups can be mono- or polyunsaturated.
Halogen is generally fluorine, chlorine, bromine or iodine. This
also applies, correspondingly, to halogen in combination with other
meanings, such as haloalkyl or halophenyl.
Haloalkyl groups preferably have a chain length of from 1 to 6
carbon atoms. Haloalkyl is, for example, fluoromethyl,
difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl,
trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl,
2-chloroethyl, pentafluoroethyl, 1,1-difluoro-2,2,2-trichloroethyl,
2,2,3,3-tetrafluoroethyl and 2,2,2-trichloroethyl.
Alkoxy is, for example, methoxy, ethoxy, propoxy, i-propoxy,
n-butoxy, isobutoxy, sec-butoxy and tert-butoxy and also the
isomeric pentyloxy and hexyloxy radicals.
Alkoxyalkyl groups preferably have a chain length of 1 to 6 carbon
atoms.
Alkoxyalkyl is, for example, methoxymethyl, methoxyethyl,
ethoxymethyl, ethoxyethyl, n-propoxymethyl, n-propoxyethyl,
isopropoxymethyl or isopropoxyethyl.
Alkoxycarbonyl is for example methoxycarbonyl (which is
C.sub.1alkoxycarbonyl), ethoxycarbonyl, propoxycarbonyl,
isopropoxycarbonyl, n-butoxycarbonyl, tert-butoxycarbonyl,
n-pentoxycarbonyl or hexoxycarbonyl.
The cycloalkyl groups preferably have from 3 to 6 ring carbon
atoms, for example cyclopropyl, cyclobutyl, cyclopentyl and
cyclohexyl.
As used herein, the term "C.sub.2-C.sub.6alkynyl" refers to a
straight or branched hydrocarbon chain radical group consisting
solely of carbon and hydrogen atoms, containing at least one triple
bond, having from two to six carbon atoms, and which is attached to
the rest of the molecule by a single bond. The term
"C.sub.2-C.sub.4 alkynyl" and "C.sub.2-C.sub.3alkynyl" are to be
construed accordingly. Examples of C.sub.2-C.sub.6alkynyl include,
but are not limited to, ethynyl, prop-1-ynyl, but-1-ynyl,
but-2-ynyl.
As used herein, the term "C.sub.2-C.sub.6alkenyl" refers to a
straight or branched hydrocarbon chain radical group consisting
solely of carbon and hydrogen atoms, containing at least one double
bond, having from two to six carbon atoms, and which is attached to
the rest of the molecule by a single bond. The term
"C.sub.2-C.sub.4 alkenyl" and "C.sub.2-C.sub.3alkenyl" are to be
construed accordingly. Examples of C.sub.2-C.sub.6alkenyl include,
but are not limited to, prop-1-enyl, but-1-enyl, but-2-enyl.
In the context of this invention "L.sub.1, L.sub.2, L.sub.3 and
L.sub.4 form together with the two carbon atoms to which L.sub.1
and L.sub.4 are attached or to which L.sub.1 and L.sub.3 are
attached when L.sub.4 is bond, an aromatic or partially saturated
carbocyclic ring system", the carbocyclic ring system is preferably
a group having 5 to 6 ring carbon atoms which are unsaturated or
partially saturated, for example, but are not limited to phenyl and
cyclohexenyl.
In the context of this invention "L.sub.1, L.sub.2, L.sub.3 and
L.sub.4 form together with the two carbon atoms to which L.sub.1
and L.sub.4 are attached or to which L.sub.1 and L.sub.3 are
attached when L.sub.4 is bond, an aromatic or partially saturated
heterocyclic ring system", the heterocyclic ring system is
preferably a group comprising 1 to 3 heteroatoms in the ring, which
are unsaturated or partially saturated, for example, but are not
limited to pyrrolyl; pyrazolyl; isoxazolyl; furanyl; thienyl;
imidazolyl; oxazolyl; thiazolyl; isothiazolyl; triazolyl;
oxadiazolyl; thiadiazolyl; tetrazolyl; furyl; pyridyl; pyrimidyl;
pyrazinyl; pyridazinyl; triazinyl, pyranyl; pyrrolidinyl,
piperidinyl; pyrrolidinyl-2-one; piperidinyl-2-one.
In the context of this invention "mono- to polysubstituted" in the
definition of the substituents, means typically, depending on the
chemical structure of the substituents, monosubstituted to
seven-times substituted, preferably monosubstituted to five-times
substituted, more preferably mono-, di- or tri-substituted.
An example for an aromatic or partially saturated carbocyclic or
heterocyclic ring system wherein one of R.sub.10a, R.sub.10b,
R.sub.10c or R.sub.10d can represent oxo, is the group
J.sub.15:
##STR00003## wherein X, R.sub.1 and A are as defined under formula
I above.
The compounds of formula I according to the invention also include
hydrates which may be formed during the salt formation.
Compounds of formula I are preferred, wherein
R.sub.1 is C.sub.1-C.sub.4alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl,
C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl; or is
C.sub.3-C.sub.6cycloalkyl mono- or polysubstituted by substituents
selected from the group consisting of halogen, cyano and
C.sub.1-C.sub.4alkyl; or is
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl mono- or
polysubstituted by substituents selected from the group consisting
of halogen, cyano and C.sub.1-C.sub.4alkyl;
R.sub.2 is hydrogen, halogen, C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
O(C.sub.1-C.sub.4haloalkyl), --SF.sub.5,
--C(O)C.sub.1-C.sub.4haloalkyl, cyano, C.sub.1-C.sub.6haloalkyl or
is C.sub.1-C.sub.6haloalkyl substituted by one or two substituents
selected from the group consisting of hydroxyl, methoxy and cyano;
or is C.sub.3-C.sub.6cycloalkyl which can be mono- or
polysubstituted by substituents selected from the group consisting
of halogen, cyano and C.sub.1-C.sub.4alkyl;
G.sub.1 is N or CR.sub.4;
G.sub.2 is N or CR.sub.5;
G.sub.3 is O, S or NR.sub.6;
R.sub.6 is C.sub.1-C.sub.4alkyl which can be mono- or
polysubstituted by substituents selected from the group consisting
of halogen and C.sub.1-C.sub.2alkylsulfinyl;
R.sub.4 and R.sub.5, independently from each other, are hydrogen,
halogen, cyano, nitro, C.sub.1-C.sub.6alkyl,
C.sub.1-C.sub.6haloalkyl, or are C.sub.3-C.sub.6cycloalkyl which
can be mono- or polysubstituted by R.sub.8; or are
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl which can be mono-
or polysubstituted by R.sub.9; or
R.sub.4 and R.sub.5, independently from each other, are
C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.2-C.sub.6haloalkynyl,
C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkoxy,
C.sub.1-C.sub.6alkylsulfanyl, C.sub.1-C.sub.4alkylsulfonyl,
C.sub.1-C.sub.6alkylsulfinyl C.sub.1-C.sub.6haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfonyl, C.sub.1-C.sub.6haloalkylsulfinyl
or hydroxyl;
R.sub.8 and R.sub.9, independently from each other, are halogen,
nitro, cyano, C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkoxy
C.sub.1-C.sub.4alkyl or C.sub.1-C.sub.4haloalkyl; and
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 form together with the two
carbon atoms to which L.sub.1 and L.sub.4 are attached, an aromatic
or partially saturated carbocyclic or heterocyclic ring system;
wherein
L.sub.1 is nitrogen, sulfur, oxygen or C--R.sub.10a;
L.sub.2 is nitrogen, sulfur, oxygen or C--R.sub.10b;
L.sub.3 is nitrogen, sulfur, oxygen or C--R.sub.10c;
L.sub.4 is nitrogen, sulfur, oxygen, a direct bond or C--R.sub.10d;
with the provisos that no more than 2 substituents selected from
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 can be oxygen or sulfur; and
if two L groups are oxygen, they are not adjacent to each
other;
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.2-C.sub.4alkylcarbonyl, C.sub.2-C.sub.6alkoxycarbonyl or
--SF.sub.5; additionally one of R.sub.10a, R.sub.10b, R.sub.10c and
R.sub.10d can be oxo; and agrochemically acceptable salts,
stereoisomers, enantiomers, tautomers and N-oxides of those
compounds.
A preferred group of compounds of formula I is represented by the
compounds of formula I-1
##STR00004##
wherein the substituents X, A, R.sub.1, R.sub.2, R.sub.6, G.sub.3,
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as defined under formula
I above.
Embodiment (A1)
Preferred are compounds of formula I-1, wherein
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4alkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl or
C.sub.3-C.sub.6cycloalkyl;
R.sub.2 is halogen, C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4haloalkyl, cyano or is
C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by
substituents selected from the group consisting of halogen, cyano
and C.sub.1-C.sub.4alkyl;
X and G.sub.3 is as defined under formula I above;
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.3-C.sub.6cyclohaloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.2-C.sub.4alkylcarbonyl, C.sub.2-C.sub.6alkoxycarbonyl,
--SF.sub.5; additionally one of R.sub.10a, R.sub.10b, R.sub.10c and
R.sub.10d can be oxo.
Embodiment (A2)
Further preferred are compounds of formula I-1a
##STR00005##
wherein J is selected from the group consisting of
##STR00006## ##STR00007## ##STR00008## ##STR00009##
and A, G.sub.3, R.sub.1, R.sub.2, X, R.sub.10a, R.sub.10b,
R.sub.10c, R.sub.10d, are as defined under Embodiment (A1).
Embodiment (A3)
Further preferred are compounds of formula I-1a
##STR00010##
wherein J is as defined under Embodiment (A2) above and
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4alkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl or
C.sub.3-C.sub.6cycloalkyl;
R.sub.2 is halogen, C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4haloalkyl, cyano or
C.sub.3-C.sub.6cycloalkyl;
X and G.sub.3 is as defined under formula I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.3-C.sub.6cyclohaloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl or
C.sub.1-C.sub.4haloalkylsulfonyl.
Embodiment (A4)
Further preferred are compounds of formula I-1a
##STR00011##
wherein J is as defined under Embodiment (A2) above and
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4alkyl;
R.sub.2 is C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.4haloalkoxy or C.sub.1-C.sub.4haloalkyl;
X is as defined under formula I above; and
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.3-C.sub.6cyclohaloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl or
C.sub.1-C.sub.4haloalkylsulfonyl.
Embodiment (A5)
Further preferred are compounds of formula I-1a
##STR00012##
wherein J is as defined under Embodiment (A2) above and
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4 alkyl;
R.sub.2 is --OCF.sub.3, --SCF.sub.3, --S(O)CF.sub.3,
--S(O).sub.2CF.sub.3 or CF.sub.3;
X is as defined under formula I above; and
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl,
C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl,
C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.4alkoxy,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio,
C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl,
C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl or
C.sub.1-C.sub.4haloalkylsulfonyl.
Embodiment (A6)
Further preferred are compounds of formula I-1a
##STR00013##
wherein J is as defined under Embodiment (A2) above and
A is C--H or N;
R.sub.1 is ethyl;
R.sub.2 is CF.sub.3;
X is as defined under formula I above; and
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, Br, Cl, I, F, cyano, methyl, ethyl,
isopropyl, propyl, trifluoromethyl, CF.sub.3CH.sub.2--, CH.sub.3O,
--SCF.sub.3, --S(O)CF.sub.3 or --S(O).sub.2CF.sub.3.
Embodiment (A7)
Further preferred are compounds of formula I-1a
##STR00014##
wherein J is as defined under Embodiment (A2) above and
A is C--H or N;
R.sub.1 is ethyl;
R.sub.2 is CF.sub.3;
X is as defined under formula I above;
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, Br, Cl, I, F, cyano, methyl, or
CF.sub.3.
Embodiment (A8)
Further preferred are compounds of formula I-1a
##STR00015##
wherein J is as defined under Embodiment (A2) and
A is C--H or N;
R.sub.1 is ethyl;
R.sub.2 is CF.sub.3;
X is as defined under formula I above;
G.sub.3 is N--R.sub.6, R.sub.6 is as defined under formula I
above;
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen in all groups J except J.sub.2; and
R.sub.10a, R.sub.10b and R.sub.10d, independently from each other,
are hydrogen in J.sub.2 and R.sub.10c is methyl in J.sub.2.
In all of the preferred embodiments of formula I-1 above, X is
preferably S or SO.sub.2 and, independently from the definition of
X, R.sub.6 is methyl.
A further preferred group of compounds of formula I is represented
by the compounds of formula I-2
##STR00016##
wherein the substituents X, A, R.sub.1, R.sub.2, R.sub.6, G.sub.3,
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as defined under formula
I above.
Embodiment (B1)
Preferred are compounds of formula I-2, wherein
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4alkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl or
C.sub.3-C.sub.6cycloalkyl;
R.sub.2 is halogen, C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4haloalkyl, cyano or is
C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by
substituents selected from the group consisting of halogen, cyano
and C.sub.1-C.sub.4alkyl;
X and G.sub.3 is as defined under formula I above;
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.3-C.sub.6cyclohaloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.2-C.sub.4alkylcarbonyl, C.sub.2-C.sub.6alkoxycarbonyl,
--SF.sub.5; additionally one of R.sub.10a, R.sub.10b, R.sub.10c and
R.sub.10d can be oxo.
Embodiment (B2)
Further preferred are compounds of formula I-2a
##STR00017##
wherein J is selected from the group consisting of
##STR00018## ##STR00019## ##STR00020## ##STR00021##
and A, G.sub.3, R.sub.1, R.sub.2, X, R.sub.10a, R.sub.10b,
R.sub.10c, R.sub.10d, are as defined under Embodiment (B1).
Embodiment (B3)
Further preferred are compounds of formula I-2a
##STR00022##
wherein J is as defined under Embodiment (B2) and
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4alkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl or
C.sub.3-C.sub.6cycloalkyl;
R.sub.2 is halogen, C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4haloalkyl, cyano or
C.sub.3-C.sub.6cycloalkyl;
X and G.sub.3 is as defined under formula I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.3-C.sub.6cyclohaloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl or
C.sub.1-C.sub.4haloalkylsulfonyl.
Embodiment (B4)
Further preferred are compounds of formula I-2a
##STR00023##
wherein J is as defined under Embodiment (B2) and
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4alkyl;
R.sub.2 is C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.4haloalkoxy or C.sub.1-C.sub.4haloalkyl;
X is as defined under formula I above; and
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.3-C.sub.6cyclohaloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl or
C.sub.1-C.sub.4haloalkylsulfonyl.
Embodiment (B5)
Further preferred are compounds of formula I-2a
##STR00024##
wherein J is as defined under Embodiment (B2) and
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4 alkyl;
R.sub.2 is --OCF.sub.3, --SCF.sub.3, --S(O)CF.sub.3,
--S(O).sub.2CF.sub.3 or CF.sub.3;
X is as defined under formula I above; and
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl,
C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl,
C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.4alkoxy,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio,
C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl,
C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl or
C.sub.1-C.sub.4haloalkylsulfonyl.
Embodiment (B6)
Further preferred are compounds of formula I-2a
##STR00025##
wherein J is as defined under Embodiment (B2) and
A is C--H or N;
R.sub.1 is ethyl;
R.sub.2 is CF.sub.3;
X is as defined under formula I above; and
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, Br, Cl, I, F, cyano, methyl, ethyl,
isopropyl, propyl, CF.sub.3, CF.sub.3CH.sub.2--, CH.sub.3O,
--SCF.sub.3, --S(O)CF.sub.3 or --S(O).sub.2CF.sub.3.
Embodiment (B7)
Further preferred are compounds of formula I-2a
##STR00026##
wherein J is as defined under Embodiment (B2) and
A is C--H or N;
R.sub.1 is ethyl;
R.sub.2 is CF.sub.3;
X is as defined under formula I above;
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, Br, Cl, I, F, cyano, methyl, or
CF.sub.3.
Embodiment (B8)
Further preferred are compounds of formula I-2a
##STR00027##
wherein J is as defined under Embodiment (B2) and
A is C--H or N;
R.sub.1 is ethyl;
R.sub.2 is CF.sub.3;
X is as defined under formula I above;
G.sub.3 is N--R.sub.6, R.sub.6 is as defined under formula I
above;
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen in all groups J except J.sub.2; and
R.sub.10a, R.sub.10b, and R.sub.10d, independently from each other,
are hydrogen in J.sub.2 and R.sub.10c is methyl in J.sub.2.
In all of the preferred embodiments of formula I-2 above, X is
preferably S or SO.sub.2 and independently from the definition of
X, R.sub.6 is methyl.
A further preferred group of compounds of formula I is represented
by the compounds of formula I-3
##STR00028##
wherein the substituents X, A, R.sub.1, R.sub.2, R.sub.6, G.sub.3,
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as defined under formula
I above.
Embodiment (C1)
Preferred are compounds of formula I-3, wherein
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4alkyl,
C.sub.3-C.sub.6Cycloalkyl-C.sub.1-C.sub.4alkyl or
C.sub.3-C.sub.6Cycloalkyl;
R.sub.2 is halogen, C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4haloalkyl, cyano or is
C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by
substituents selected from the group consisting of halogen, cyano
and C.sub.1-C.sub.4alkyl;
X and G.sub.3 is as defined under formula I above;
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.3-C.sub.6cyclohaloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.2-C.sub.4alkylcarbonyl, C.sub.2-C.sub.6alkoxycarbonyl,
--SF.sub.5; additionally one of R.sub.10a, R.sub.10b, R.sub.10c and
R.sub.10d can be oxo.
Embodiment (C2)
Further preferred are compounds of formula I-3a
##STR00029##
wherein J is selected from the group consisting of
##STR00030## ##STR00031## ##STR00032## ##STR00033##
and A, G.sub.3, R.sub.1, R.sub.2, X, R.sub.10a, R.sub.10b,
R.sub.10c, R.sub.10d, are as defined under Embodiment (C1).
Embodiment (C3)
Further preferred are compounds of formula I-3a
##STR00034##
wherein J is as defined under Embodiment (C2) and
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4alkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl or
C.sub.3-C.sub.6cycloalkyl;
R.sub.2 is halogen, C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4haloalkyl, cyano or
C.sub.3-C.sub.6cycloalkyl;
X and G.sub.3 is as defined under formula I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.3-C.sub.6cyclohaloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl or
C.sub.1-C.sub.4haloalkylsulfonyl.
Embodiment (C4)
Further preferred are compounds of formula I-3a
##STR00035##
wherein J is as defined under Embodiment (C2) and
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4alkyl;
R.sub.2 is C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.4haloalkoxy or C.sub.1-C.sub.4haloalkyl;
X is as defined under formula I above; and
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.3-C.sub.6cyclohaloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl or
C.sub.1-C.sub.4haloalkylsulfonyl.
Embodiment (C5)
Further preferred are compounds of formula I-3a
##STR00036##
wherein J is as defined under Embodiment (C2) and
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4 alkyl;
R.sub.2 is --OCF.sub.3, --SCF.sub.3, --S(O)CF.sub.3,
--S(O).sub.2CF.sub.3 or CF.sub.3;
X is as defined under formula I above; and
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl,
C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl,
C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.4alkoxy,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio,
C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl,
C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl or
C.sub.1-C.sub.4haloalkylsulfonyl.
Embodiment (C6)
Further preferred are compounds of formula I-3a
##STR00037##
wherein J is as defined under Embodiment (C2) and
A is C--H or N;
R.sub.1 is ethyl;
R.sub.2 is CF.sub.3;
X is as defined under formula I above; and
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, Br, Cl, I, F, cyano, methyl, ethyl,
isopropyl, propyl, CF.sub.3, CF.sub.3CH.sub.2--, CH.sub.3O,
--SCF.sub.3, --S(O)CF.sub.3 or --S(O).sub.2CF.sub.3.
Embodiment (C7)
Further preferred are compounds of formula I-3a
##STR00038##
wherein J is as defined under Embodiment (C2) and
A is C--H or N;
R.sub.1 is ethyl;
R.sub.2 is CF.sub.3;
X is as defined under formula I above;
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, Br, Cl, I, F, cyano, methyl, or
CF.sub.3.
Embodiment (C8)
Further preferred are compounds of formula I-3a
##STR00039##
wherein J is as defined under Embodiment (C2) and
A is C--H or N;
R.sub.1 is ethyl;
R.sub.2 is CF.sub.3;
X is as defined under formula I above;
G.sub.3 is N--R.sub.6, R.sub.6 is as defined under formula I
above;
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen in all groups J except J.sub.2; and
R.sub.10a, R.sub.10b, and R.sub.10d, independently from each other,
are hydrogen in J.sub.2 and R.sub.10c is methyl in J.sub.2.
In all of the preferred embodiments of formula I-3 above, X is
preferably S or SO.sub.2 and independently from the definition of
X, R.sub.6 is methyl.
A further preferred group of compounds of formula I is represented
by the compounds of formula I-4
##STR00040##
wherein the substituents X, A, R.sub.1, R.sub.2, R.sub.6, G.sub.3,
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as defined under formula
I above.
Embodiment (D1)
Preferred are compounds of formula I-4, wherein
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4alkyl,
C.sub.3-C.sub.6Cycloalkyl-C.sub.1-C.sub.4alkyl or
C.sub.3-C.sub.6Cycloalkyl;
R.sub.2 is halogen, C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4haloalkyl, cyano or is
C.sub.3-C.sub.6cycloalkyl which can be mono- or polysubstituted by
substituents selected from the group consisting of halogen, cyano
and C.sub.1-C.sub.4alkyl;
X and G.sub.3 is as defined under formula I above;
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.3-C.sub.6cyclohaloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.2-C.sub.4alkylcarbonyl, C.sub.2-C.sub.6alkoxycarbonyl,
--SF.sub.5; additionally one of R.sub.10a, R.sub.10b, R.sub.10c and
R.sub.10d can be oxo.
Embodiment (D2)
Further preferred are compounds of formula I-4a
##STR00041##
wherein J is selected from the group consisting of
##STR00042## ##STR00043## ##STR00044## ##STR00045##
and A, G.sub.3, R.sub.1, R.sub.2, X, R.sub.10a, R.sub.10b,
R.sub.10c, R.sub.10d, are as defined under Embodiment (D1).
Embodiment (D3)
Further preferred are compounds of formula I-4a
##STR00046##
wherein J is as defined under Embodiment (D2) and
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4alkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4alkyl or
C.sub.3-C.sub.6cycloalkyl;
R.sub.2 is halogen, C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4haloalkyl, cyano or
C.sub.3-C.sub.6cycloalkyl;
X and G.sub.3 is as defined under formula I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.3-C.sub.6cyclohaloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl or
C.sub.1-C.sub.4haloalkylsulfonyl.
Embodiment (4)
Further preferred are compounds of formula I-4a
##STR00047##
wherein J is as defined under Embodiment (D2) and
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4alkyl;
R.sub.2 is C.sub.1-C.sub.4haloalkylsulfanyl,
C.sub.1-C.sub.4haloalkylsulfinyl, C.sub.1-C.sub.4haloalkylsulfonyl,
C.sub.1-C.sub.4haloalkoxy or C.sub.1-C.sub.4haloalkyl;
X is as defined under formula I above; and
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, nitro, cyano, hydroxyl,
C.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl,
C.sub.2-C.sub.6alkynyl, C.sub.3-C.sub.6cycloalkyl,
C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6haloalkenyl,
C.sub.2-C.sub.6haloalkynyl, C.sub.3-C.sub.6halocycloalkyl,
C.sub.3-C.sub.6cyclohaloalkyl-C.sub.1-C.sub.4 cycloalkyl,
C.sub.1-C.sub.4alkoxy, C.sub.1-C.sub.4haloalkoxy,
C.sub.1-C.sub.4alkylthio, C.sub.1-C.sub.4alkylsulfinyl,
C.sub.1-C.sub.4alkylsulfonyl, C.sub.1-C.sub.4haloalkylthio,
C.sub.1-C.sub.4haloalkylsulfinyl or
C.sub.1-C.sub.4haloalkylsulfonyl.
Embodiment (D5)
Further preferred are compounds of formula I-4a
##STR00048##
wherein J is as defined under Embodiment (D2) and
A is C--H or N;
R.sub.1 is C.sub.1-C.sub.4 alkyl;
R.sub.2 is --OCF.sub.3, --SCF.sub.3, --S(O)CF.sub.3,
--S(O).sub.2CF.sub.3 or CF.sub.3;
X is as defined under formula I above; and
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl,
C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl,
C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.4alkoxy,
C.sub.1-C.sub.4haloalkoxy, C.sub.1-C.sub.4alkylthio,
C.sub.1-C.sub.4alkylsulfinyl, C.sub.1-C.sub.4alkylsulfonyl,
C.sub.1-C.sub.4haloalkylthio, C.sub.1-C.sub.4haloalkylsulfinyl or
C.sub.1-C.sub.4haloalkylsulfonyl.
Embodiment (D6)
Further preferred are compounds of formula I-4a
##STR00049##
wherein J is as defined under Embodiment (D2) and
A is C--H or N;
R.sub.1 is ethyl;
R.sub.2 is CF.sub.3;
X is as defined under formula I above; and
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, Br, Cl, I, F, cyano, methyl, ethyl,
isopropyl, propyl, CF.sub.3, CF.sub.3CH.sub.2--, CH.sub.3O,
--SCF.sub.3, --S(O)CF.sub.3 or --S(O).sub.2CF.sub.3.
Embodiment (D7)
Further preferred are compounds of formula I-4a
##STR00050##
wherein J is as defined under Embodiment (D2) and
A is C--H or N;
R.sub.1 is ethyl;
R.sub.2 is CF.sub.3;
X is as defined under formula I above;
G.sub.3 is N--R.sub.6, wherein R.sub.6 is as defined under formula
I above; and
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen, Br, Cl, I, F, cyano, methyl, or
CF.sub.3.
Embodiment (D8)
Further preferred are compounds of formula I-4a
##STR00051##
wherein J is as defined under Embodiment (D2) and
A is C--H or N;
R.sub.1 is ethyl;
R.sub.2 is CF.sub.3;
X is as defined under formula I above;
G.sub.3 is N--R.sub.6, R.sub.6 is as defined under formula I
above;
R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently from
each other, are hydrogen in all groups J except J.sub.2; and
R.sub.10a, R.sub.10b, and R.sub.10d, independently from each other,
are hydrogen in J.sub.2 and R.sub.10c is methyl in J.sub.2.
In all of the preferred embodiments of formula I-4 above, X is
preferably S or SO.sub.2 and independently from the definition of
X, R.sub.6 is methyl.
In all of the preferred embodiments A2-A8, B2-B8, C2-C8 and D2-D8,
J is preferably J.sub.1, J.sub.2, J.sub.3, J.sub.4, J.sub.5,
J.sub.6, J.sub.12, J.sub.17, J.sub.18, J.sub.24, J.sub.19, J.sub.20
or J.sub.23, in particular J is J.sub.1.
Further preferred compounds of formula I are represented by the
compounds of formula I-5a
##STR00052##
wherein
G.sub.1 is N or CH;
G.sub.2 is N or CH;
R.sub.2 is C.sub.1-C.sub.4haloalkyl;
A is N or CH;
R.sub.6 is C.sub.1-C.sub.4alkyl;
X is S or SO.sub.2;
R.sub.1 is C.sub.1-C.sub.4alkyl; and
Ja is selected from the group consisting of
##STR00053## ##STR00054##
and R.sub.10a, R.sub.10b, R.sub.10c, and R.sub.10d, independently
from each other, are hydrogen, halogen, cyano, cyclopropyl,
C.sub.1-C.sub.4 alkyl or C.sub.1-C.sub.4 haloalkyl.
In especially preferred compounds of formula I
##STR00055##
R.sub.1 is C.sub.1-C.sub.4alkyl;
R.sub.2 is C.sub.1-C.sub.4haloalkyl;
X is S or SO.sub.2;
A is CH or N;
G.sub.1 is CH or N;
G.sub.2 is CH or N;
G.sub.3 is N(C.sub.1-C.sub.4alkyl);
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 form together with the two
carbon atoms to which L.sub.1 and L.sub.4 are attached, an aromatic
or partially saturated carbocyclic or heterocyclic ring system;
wherein
L.sub.1 is CH, NH, N--C.sub.1-C.sub.4alkyl or S;
L.sub.2 is CH, C(C.sub.1-C.sub.4alkyl),
C(C.sub.1-C.sub.4haloalkyl), N or S;
L.sub.3 is CH, N or N--C.sub.1-C.sub.4alkyl; and
L.sub.4 is absent or N;
with the proviso that no more than three L groups can be
nitrogen.
In especially preferred compounds of formula I-5a
##STR00056##
G.sub.1 is N or CH;
G.sub.2 is N or CH;
R.sub.2 is C.sub.1-C.sub.4haloalkyl,
C.sub.1-C.sub.4haloalkylsulfanyl or
C.sub.1-C.sub.4haloalkylsulfinyl;
A is N or CH;
R.sub.6 is C.sub.1-C.sub.4alkyl;
X is S or SO.sub.2;
R.sub.1 is C.sub.1-C.sub.4alkyl; and
Ja is selected from the group consisting of
##STR00057## ##STR00058##
in particular from J.sub.1a, J.sub.23a, J.sub.23b, J.sub.6,
J.sub.20, J.sub.1b, J.sub.12, J.sub.17, J.sub.18, and J.sub.24,
most preferred J.sub.1a, J.sub.23a, J.sub.23b, J.sub.6, J.sub.20,
J.sub.12, J.sub.17, J.sub.18, and J.sub.24;
wherein R.sub.10a; R.sub.10b, R.sub.10c, and R.sub.10d;
independently from each other, are selected from the group
consisting of hydrogen, halogen, cyano cyclopropyl, C.sub.1-C.sub.4
alkyl and C.sub.1-C.sub.4 haloalkyl.
The process according to the invention for preparing compounds of
formula (I) is carried out by methods known to those skilled in the
art, or described for example in WO 2009/131237,
WO 2011/043404, WO 2011/040629, WO 2010/125985, WO 2012/086848, WO
2013/018928, WO 2013/191113, WO 2013/180193 and WO 2013/180194, and
involves reaction of a compound of formula II,
##STR00059##
wherein Q is the group
##STR00060##
wherein Z is X--R.sub.1 or a leaving group, for example a halogen,
and wherein X, R.sub.1, L.sub.1, L.sub.2, L.sub.3, L.sub.4 and A
are as described under formula I above, and wherein the arrow in
the radical Q shows the point of attachment to the carbon atom of
the carboxyl group in the compound of formula II,
with a compound of formula III,
##STR00061##
wherein R.sub.6, R.sub.2, G.sub.1 and G.sub.2 are as described
under formula I above and wherein X.sub.1 is OH, SH or NH--R.sub.6,
in the presence of a dehydrating agent, such as for example
polyphosphoric acid at temperature between 150.degree. C. to
250.degree. C., to yield compounds of formula Ia, wherein the
substituents are as described above and under formula I.
Such processes are well known and have been described for example
in WO 2008/128968 or WO 2006/003440. The process is summarized in
scheme 1 for compounds of formula Ia:
##STR00062##
As can be seen in scheme 1, the formation of compounds of formula
Ia, wherein R.sub.2, G.sub.1, G.sub.2 and G.sub.3 are as described
in compounds of formula I, occurs through the intermediacy of a
compound of formula IV (and/or its position isomer Iva).
Intermediate IV or intermediate IVa may form as a pure entity, or
intermediates IV and IVa may arise as a mixture of regioisomeric
acylation products. It is in many cases advantageous to thus
prepare compounds of formula (I) through such intermediates IV/IVa,
which may be isolated and optionally purified. This is illustrated
for compounds of formula Ia in scheme 2:
##STR00063##
Compounds of the formula IV and/or IVa (or a mixture thereof), or a
salt thereof, wherein Q is as defined above, and wherein R.sub.6,
R.sub.2, G.sub.1, G.sub.2 and G.sub.3 are as described under
formula I above and X.sub.1 are as described before, may be
prepared by
i) activation of compound of formula II, wherein Q is as defined
above, by methods known to those skilled in the art and described
in, for example, Tetrahedron, 2005, 61 (46), 10827-10852, to form
an activated species IIa, wherein Q is as defined above and wherein
X.sub.00 is halogen, preferably chlorine. For example, compounds
IIa where X.sub.00 is halogen, preferably chlorine, are formed by
treatment of II with, for example, oxalyl chloride (COCl).sub.2 or
thionyl chloride SOCl.sub.2 in the presence of catalytic quantities
of N,N-dimethylformamide DMF in inert solvents such as methylene
chloride CH.sub.2Cl.sub.2 or tetrahydrofuran THF at temperatures
between 20 to 100.degree. C., preferably 25.degree. C.
Alternatively, treatment of compounds of formula II with, for
example, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide EDC or
dicyclohexyl carbodiimide DCC will generate an activated species
IIa, wherein X.sub.00 is X.sub.01 or X.sub.02 respectively, in an
inert solvent, such as pyridine or tetrahydrofuran THF, optionally
in the presence of a base, such as triethylamine, at temperatures
between 25-180.degree. C.; followed by
ii) treatment of the activated species IIa with a compound of
formula III (or a salt thereof), wherein R.sub.6, R.sub.2, G.sub.1
and G.sub.2 are as described under formula I above, optionally in
the presence of a base, such as triethylamine or pyridine, in an
inert solvents such as dichloromethane, tetrahydrofuran, dioxane or
toluene, at temperatures between 0 and 80.degree. C., to form the
compounds of formula IV and/or IVa (or a mixture thereof).
Compounds of formula IV and/or IVa (or a mixture thereof) may
further be converted into compounds of formula Ia, wherein Q is as
defined above, and wherein R.sub.6, R.sub.2, G.sub.1, G.sub.2 and
G.sub.3 are as described under formula I above, by dehydration, eg.
by heating the compounds IV and/or IVa (or a mixture thereof) in
the presence of an acid catalyst, such as for example methane
sulfonic acid, or para-toluene sulfonic acid TsOH, in an inert
solvent such as N-methyl pyrrolidine NMP at temperatures between
25-180.degree. C., preferably 100-170.degree. C., optionally under
microwave conditions. Such processes have been described
previously, for example, in WO 2010/125985.
Compounds of formula Ia, wherein Q is as defined above, and wherein
Z is a leaving group, for example halogen, preferably fluorine or
chlorine, and wherein R.sub.6, R.sub.2, G.sub.1, G.sub.3 and
G.sub.2 are as described under formula I above, can be reacted with
compounds of formula V R.sub.1--SH (V),
or a salt thereof, wherein R.sub.1 is as defined in formula I,
optionally in the presence of a suitable base, such as alkali metal
carbonates, for example sodium carbonate and potassium carbonate,
or alkali metal hydrides such as sodium hydride, or alkali metal
hydroxides such as sodium hydroxide and potassium hydroxide, in an
inert solvent at temperatures preferably between 25-120.degree. C.,
to generate compounds of formula Ib, wherein R.sub.1 is as
described under formula I above, and in which R.sub.6, A, R.sub.2,
L.sub.1, L.sub.2, L.sub.3, L.sub.4, G.sub.1, G.sub.2 and G.sub.3
are as described under formula I above. Examples of solvent to be
used include ethers such as THF, ethylene glycol dimethyl ether,
tert-butylmethyl ether, and 1,4-dioxane, aromatic hydrocarbons such
as toluene and xylene, nitriles such as acetonitrile or polar
aprotic solvents such as N,N-dimethylformamide,
N,N-dimethylacetamide, N-methyl-2-pyrrolidone or dimethyl
sulfoxide. Similar chemistry has been previously described, as for
example in WO2013/018928. Examples of salts of the compound of
formula V include compounds of the formula Va R.sub.1--S-M
(Va),
wherein R.sub.1 is as defined above and wherein M is, for example,
sodium or potassium. This is illustrated for compounds of formula
Ib in scheme 3:
##STR00064##
Alternatively, this reaction can be carried out in the presence of
a palladium catalyst, such as
tris(dibenzylideneacetone)dipalladium(0), in the presence of a
phosphor ligand, such as xanthphos, in an inert solvent, for
example, xylene at temperatures between 100-160.degree. C.,
preferably 140.degree. C., as described by Perrio et al. in
Tetrahedron 2005, 61, 5253-5259.
The subgroup of compounds of formula I, wherein X is SO (sulfoxide)
and/or SO.sub.2 (sulfone), may be obtained by means of an oxidation
reaction of the corresponding sulfide compounds of formula I,
wherein X is S (i.e. a compound of formula Ib above), involving
reagents such as, for example, m-chloroperoxybenzoic acid (mCPBA),
hydrogen peroxide, oxone, sodium periodate, sodium hypochlorite or
tert-butyl hypochlorite amongst other oxidants. The oxidation
reaction is generally conducted in the presence of a solvent.
Examples of the solvent to be used in the reaction include
aliphatic halogenated hydrocarbons such as dichloromethane and
chloroform; alcohols such as methanol and ethanol; acetic acid;
water; and mixtures thereof. The amount of the oxidant to be used
in the reaction is generally 1 to 3 moles, preferably 1 to 1.2
moles, relative to 1 mole of the sulfide compounds Ib to produce
the sulfoxide compounds I (wherein X.dbd.SO), and preferably 2 to
2.2 moles of oxidant, relative to 1 mole of the sulfide compounds
Ib to produce the sulfone compounds I (wherein X.dbd.SO.sub.2).
Such oxidation reactions are disclosed, for example, in WO
2013/018928.
More specifically, Compounds of formula VIa, wherein Z is
X--R.sub.1 or a leaving group, for example halogen, and wherein X,
R.sub.1, R.sub.2, R.sub.6 and A are as described under formula I
above, wherein G.sub.1 is N, G.sub.3 is N--R.sub.6, G.sub.2 is C--H
and X.sub.1 is NHR.sub.6, may be prepared by reaction between
compounds of formula II respectively IIa, wherein Z is X--R.sub.1
or a leaving group, for example halogen, and wherein X, R.sub.1 and
A are as described under formula I above, and in which X.sub.00 is
as described above, and compounds of formula IIIa, wherein R.sub.6
and R.sub.2 are as described under formula I above, under similar
conditions as for the preparation of compounds of formula Ia from
compounds of formula II/IIa and III described above (see scheme 1
and 2). This is illustrated for compounds of formula VIa in scheme
4:
##STR00065##
Analogeusly to descriptions in schemes 1 and 2, the formation of
compounds of formula VIa occurs through the intermediacy of
compounds of formula IV-1 and/or IV-1a (or a mixture thereof), or
salts thereof, which optionally may be isolated and purified.
Compounds of the formula IIIa, wherein R.sub.6, and R.sub.2 are as
described under formula I above, may be prepared from diamino
compounds of formula VII, wherein R.sub.2 is as described under
formula I above, by means of a direct alkylation with
R.sub.6--X.sub.LG, wherein R.sub.6 is as described under formula I
above and wherein X.sub.LG is a leaving group, such as halogen,
preferably iodine, bromine or chlorine, in presence of a base, such
as sodium carbonate, potassium carbonate or cesium carbonate, or
sodium hydride, in an appropriate solvent such as for example
N,N-dimethylformamide, N,N-dimethylacetamide or acetonitrile
(scheme 5).
##STR00066##
Alternatively, the sequence to prepare compounds of formula IIIa
from compounds of formula VII, may involve i. a selective acylation
of compound VII to form a compound of formula VIII, wherein R.sub.2
is as described under formula I above and wherein the acylation
agent is for example di-tert-butyl dicarbonate (leading to compound
VIII wherein R.sub.G is tert-butyloxy), in an ether solvent, such
as for example, tetrahydrofuran or dioxane; ii. alkylation of
compound VIII with R.sub.6--X.sub.LG, wherein R.sub.6 is as
described under formula I above and wherein X.sub.LG is a leaving
group, such as halogen, preferably iodine, bromine or chlorine, in
presence of a base, such as sodium carbonate, potassium carbonate
or cesium carbonate, or sodium hydride, in an appropriate solvent
such as for example N,N-dimethylformamide, N,N-dimethylacetamide or
acetonitrile, to generate a compound of formula IX, wherein R.sub.6
and R.sub.2 are as described under formula I above and wherein
R.sub.G is for example tert-butyloxy; and finally iii. deacylation
of compound IX to form the compound of formula IIIa, wherein
R.sub.6, and R.sub.2 are as described under formula I above. When
R.sub.G is for example tert-butyloxy, conditions for the acyl group
removal include, for example, treatment of compound IX with
hydrogen halide, in particular hydrogen chloride or hydrogen
bromide, in solvents such as ethers (for example diethyl ether,
tetrahydrofuran or dioxane) or acetic acid. Alternatively, compound
IX may also be treated with, for example, trifluoroacetic acid, in
optional presence of an inert solvent, such as for example
dichloromethane or chloroform, to form a compound of formula
IIIa.
This alternative approach to prepare compounds of formula IIIa is
described in more details in scheme 6 for the particular situation
where R.sub.2 is CF.sub.3, R.sub.6 is CH.sub.3, and R.sub.G is
tert-butyloxy:
##STR00067##
Diamino compounds of formula (VII) are either known, commercially
available or may be made by methods known to a person skilled in
the art, for example in analogy to a preparation method described
in U.S. Pat. No. 7,767,687.
Diamino compounds of formula IIIb and IIIc, Where in X.sub.1 is OH,
SH or NH--R.sub.6
##STR00068##
are either known, commercially available or may be made by methods
known to a person skilled in the art.
Compounds of formula II,
##STR00069##
wherein Z is X--R.sub.1 or a leaving group or a group that could be
transformed in leaving group such as, for example halogen, amine or
nitro, and wherein X, R.sub.1, L.sub.1, L.sub.2, L.sub.3, L.sub.4
and A are as described under formula I above, may be either known,
commercially available or may be made by methods known to a person
skilled in the art.
Compounds of formula IIc, wherein Q is as defined above, and
wherein Z is a leaving group, for example halogen, preferably
fluorine, chlorine, and wherein A, L.sub.1, L.sub.2, L.sub.3 and
L.sub.4 are as described under formula I above, and wherein R is
alkyl or hydrogen can be reacted with compounds of formula V
R.sub.1--SH (V),
or a salt thereof, wherein R.sub.1 is as defined in formula I,
optionally in the presence of a suitable base, such as alkali metal
carbonates, for example sodium carbonate and potassium carbonate,
or alkali metal hydrides such as sodium hydride, or alkali metal
hydroxides such as sodium hydroxide and potassium hydroxide, in an
inert solvent at temperatures preferably between 25-120.degree. C.,
to generate compounds of formula IId, wherein R is alkyl or
hydrogen, R.sub.1 is as described under formula I above, and in
which A, L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as described
under formula I above. Examples of solvent to be used include
ethers such as THF, ethylene glycol dimethyl ether,
tert-butylmethyl ether, and 1,4-dioxane, aromatic hydrocarbons such
as toluene and xylene, nitriles such as acetonitrile or polar
aprotic solvents such as N,N-dimethylformamide,
N,N-dimethylacetamide, N-methyl-2-pyrrolidone or dimethyl
sulfoxide. Examples of salts of the compound of formula V include
compounds of the formula Va R.sub.1--S-M (Va),
wherein R.sub.1 is as defined above and wherein M is, for example,
sodium or potassium. This is illustrated for compounds of formula
IId in scheme 9:
##STR00070##
Alternatively, compounds of formula IIc, wherein Z is a amine and
wherein A, L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as described
under formula I above, and wherein R is alkyl or hydrogen can be
transformed to compounds of formula IId via diazotation and
reaction with dialkyldisulfide. This transformation is well known
and could be made by methods known to a person skilled in the art
(see for example: Synthetic Communications, 31 (12), 1857-1861;
2001 or Organic & Biomolecular Chemistry, 6 (4), 745-761;
2008). Compounds of formula IIc, wherein Z is a amine and wherein
A, L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as described under
formula I above, and wherein R is alkyl or hydrogen can be
transformed to compounds of formula lie via diazotation and
reaction with sodium sulphide, followed by reduction. This
transformation is well known and could be made by methods known to
a person skilled in the art (see for example: US 20040116734 or
Chemische Berichte, 120 (7), 1151-73; 1987). Alkylation of compound
lie with R.sub.1--X.sub.LG, wherein R.sub.1 is as described under
formula I above and wherein X.sub.LG is a leaving group, such as
halogen, preferably iodine, bromine or chlorine, in presence of a
base, such as sodium carbonate, potassium carbonate or cesium
carbonate, or sodium hydride, in a appropriate solvent such as for
example N,N-dimethylformamide, N,N-dimethylacetamide or
acetonitrile, to generate a compound of formula IId, wherein
R.sub.1 is as described under formula I above. See scheme 10.
##STR00071##
Compound of formula (ii) may be prepared by reaction of a compound
of formula (IId), wherein R is alkyl via hydrolysis. For instance,
in the case where R is methyl or ethyl, the hydrolysis can be done
with water and a base, such as potassium hydroxide or lithium
hydroxide, in the absence or in the presence of a solvent, such as,
for instance, tetrahydrofuran or methanol. In the case where R is,
for example, tert-butyl, the hydrolysis is done in the presence of
acid, such as trifluoroacetic acid or hydrochloric acid. The
reaction is carried out at a temperature of from -120.degree. C. to
+130.degree. C., preferably from -100.degree. C. to 100.degree. C.
See scheme 11.
##STR00072##
Alternatively, compound of formula II may be prepared by reaction
of a compound of formula (X) wherein Z is a leaving group as nitro
or halogen such as fluorine and wherein A, L.sub.1, L.sub.2,
L.sub.3 and L.sub.4 are as described under formula I above by
reaction of a compound of formula V or Va R.sub.1--SH (V),
R.sub.1--S-M (Va),
to give compounds of formula Xd or a salt thereof, wherein R.sub.1
is as defined in formula I, optionally in the presence of a
suitable base, such as alkali metal carbonates, for example sodium
carbonate and potassium carbonate, or alkali metal hydrides such as
sodium hydride, or alkali metal hydroxides such as sodium hydroxide
and potassium hydroxide, in an inert solvent at temperatures
preferably between 25-120.degree. C., to generate compounds of
formula XIIb, wherein R.sub.1 is as described under formula I
above, and in which A, L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as
described under formula I above. Examples of solvent to be used
include ethers such as THF, ethylene glycol dimethyl ether,
tert-butylmethyl ether, and 1,4-dioxane, aromatic hydrocarbons such
as toluene and xylene, nitriles such as acetonitrile or polar
aprotic solvents such as N,N-dimethylformamide,
N,N-dimethylacetamide, N-methyl-2-pyrrolidone or dimethyl
sulfoxide.
Examples of salts of the compound of formula V include compounds of
the formula Va R.sub.1--S-M (Va),
wherein R.sub.1 is as defined above and wherein M is, for example,
sodium or potassium. Compounds of formula II may be prepared by
hydrolysis of the cyano of compound of formula Xd in acidic or
basic conditions. This transformation is well known and could be
made by methods known to a person skilled in the art (see for
example: Comprehensive Organic Transformations: A Guide to
Functional Group Preparations. Edited by Richard C. Larock 1989 p
993, VCH publishers).
This is illustrated for compounds of formula II in scheme 12.
##STR00073##
Compounds of formula X are either known, commercially available or
may be made by methods known to a person skilled in the art.
Alternatively, compound of formula IIc, where in R is Hydrogen, may
be prepared by reaction of a compound of formula (XI) where in Z is
a leaving group as nitro or halogen such as fluorine and wherein A,
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as described under
formula I above by oxidation in presence of a oxidant such as
oxygen, hydrogen peroxide or an metal oxide such as chromium
trioxide with or without acid such as sulphuric acid with or
without metal catalyst. This transformation is well known and could
be made by methods known to a person skilled in the art (see for
example: Comprehensive Organic Transformations: A Guide to
Functional Group Preparations. Edited by Richard C. Larock 1989 p
823, VCH publishers). This is illustrated for compounds of formula
II in scheme 13.
##STR00074##
Compounds of formula XI are either known, commercially available or
may be made by methods known to a person skilled in the art.
Compound of formula IIc, wherein R is C.sub.1-C.sub.6 Alkyl, A,
L.sub.1, L.sub.2, L.sub.3 and L.sub.4 are as described under
formula I above and Z is NH.sub.2, may be prepared by reaction of a
compound of formula (XII) with a compound of formula XIII wherein,
for example X.sub.00 is an halogen such as, for example, bromide
and R is C.sub.1-C.sub.6 alkyl such as, for example, ethyl. these
reactions are known to a person skilled in the art and are, for
example described in Tetrahedron 60 (2004) 2937-2942. This is
illustrated for compounds of formula IIc in scheme 14.
##STR00075##
Alternatively synthesis of compounds of formula I (benzimidazoles
(J.sub.19 and J.sub.23) wherein: L.sub.1=N or NR.sub.10a,
L.sub.2=C--R.sub.10b, L.sub.3=N or N--R.sub.10c, L.sub.4=bond;
benzothiadiazoles (J.sub.20): L.sub.1=N, L.sub.2=S, L.sub.3=N,
L.sub.4=bond; benzothiazoles (J.sub.12): L.sub.1=N,
L.sub.2=C--R.sub.10b, L.sub.3=S, L.sub.4=bond; benzotriazoles
(J.sub.18, J.sub.17 and J.sub.24): L.sub.1=N or N--R.sub.10a,
L.sub.2=N or N--R.sub.10b, L.sub.3=N or N--R.sub.10c, L.sub.4=bond;
benzoxazoles (J.sub.25): L.sub.1=N, L.sub.2=C--R.sub.10b,
L.sub.3=O, L.sub.4=bond can be made via cyclisation of
intermediates of formulae XVI or XVII as depicted in scheme 15.
The synthesis of cyclic compounds as described in the scheme 16 is
very well known and could be made by methods known to a person
skilled in the art by analogy of what was described previously in
literature. For example, for the synthesis of benzimidazoles
starting from the intermediate type XVII see Monatshefte fuer
Chemie 2011, 142 (1), 87-91; Organic Preparations and Procedures
International 2013, 45 (1), 57-65; Organic Preparations and
Procedures International 2013, 45 (2), 162-167; Tetrahedron Letters
2007 48 (18), 3251-3254; or starting from the intermediate type
XVI, see for example Journal of Organic Chemistry 2011, 76 (23),
9577-9583 or Tetrahedron 2013, 69 (6), 1717-1719. In general
manner, see for review on the preparation of benzimidazoles: The
Chemistry of Heterocyclic Compounds; Weissberger, A., Taylor, E.
C., Eds.; Wiley-VCH: New York, N.Y., 1981; Vol. 40, pp 6-60.
For example, for the synthesis of benzothiadiazoles starting from
the intermediate type XVII see Tetrahedron 2005, 61 (46),
10975-10982. See for a more general review on the preparation and
properties of benzimidazoles: Eur. J. Org. Chem. 2013, 228-255.
For example, for the synthesis of benzotriazoles starting from the
intermediate type XVII see for example, Bioorganic & Medicinal
Chemistry 2010, 18 (24), 8457-8462, using cyclocondensation as
described in scheme 15 (e.g. AcOH, NaNO.sub.2). For a more general
review on the preparation of benzotriazoles, see, for example,
Journal Chem. Pharm. Res., 2011, 3 (6) p 375-381.
For example, for the synthesis of benzothiazoles starting from the
intermediate type XVI see for example, Journal of Combinatorial
Chemistry 2009, 11 (6), 1047-1049; Chemistry--A European Journal
2012, 18 (16), 4840-4843, S4840/1-S4840/35; or WO13066729. In
addition, synthesis of benzothiazoles are well known and could be
made easily by methods known to a person skilled in the art via
other type of intermediates see, for example, Journal of Current
Pharmaceutical Research 2010; 3 (1): 13-23.
##STR00076##
Compounds of formula XIV may be prepared by identical reaction
described in scheme 1 to 6 wherein L1 is NO.sub.2 or compounds of
formula XV may be prepared by identical reaction described in
scheme 1 to 6 wherein L.sub.1 is a protected nitrogen, for example
L.sub.1 could be pyrrolidine-2,5-dione followed by deprotection,
for example with hydrazine.
Compounds of formula Ia, Ib, and I containing an N--H as L.sub.1,
L.sub.2 or L.sub.3 could react with a alkylation agent such as
methyl iodide in presence of a base, such as potassium carbonate or
sodium hydride, to give compounds of formula Ia, Ib, and I wherein
L.sub.1, L.sub.2 or L.sub.3 is an N--CH.sub.3.
The same type of process described in the general references used
in the explanation of scheme 15 could be used, for example, on
intermediate XI, II, IIc, IId, X, Xd.
Compounds of Formula I wherein G.sub.3 is O or S can be prepared,
as described in scheme 1 and scheme 2, by reaction of a compound of
formula III, wherein X.sub.1 is SH or OH with a compound of formula
II.
##STR00077##
All of these methods are known to those skilled in the art or
described for example in WO 2011/040629 or WO 2009131237, WO
2011088990, WO2011049222 or Inorg. Chimica Acta, 358 (9),
2701-2710; 2005. The methods used for the synthesis of this type of
heterocycles are well known to those skilled in the art, for review
or information around the synthesis of these type of structure via
(XVI) or via other types of intermediates, see, for example, RSC
Advances (2014), 4 (104), 60176-60208, Pure and Applied Chemistry
(2008), 80 (4), 707-715, Chemical Science Review and Letters
(2014), 2 (6), 408-414, Tetrahedron Letters 55 (2014) 5515-5520
(and cited references), Tetrahedron (2015), 71 (4), 700-708 (and
cited references), Heterocycles (2014), 89 (6), 1441-1453 (and
cited references), Heterocycles (1994) 38, 1001, Asian Journal of
chemistry (2004) 16, No 3-4, p 1241-1260 or Chin. J. Org. Chem.
2014, Vol. 34, No 6, 1048-1060.
Compounds of formula XXa wherein X.sub.1 is OH can be produced from
compounds of formula XVIII by treatment with a base, for example
alkaline earth metal bases in water, NMP, DMF, 2-Imidazolidinone,
or mixtures thereof at temperatures between 50-100.degree. C.
Reduction of the produced XIX by methods known to those skilled in
the art, for example with a metal in acidic medium, for example Fe
in acetic acid or hydrochloric acid. Such reductions of NO.sub.2
groups have been described for example in Org. Synth.; Coll. Vol.
5: 346, 1973 to leads to compounds of formula XIIa. Similar
reactions are well known to those skilled in the art and have been
described, for example in Organic Letters, 10 (14), 3025-3028; 2008
or Bioorganic & Medicinal Chemistry Letters, 16 (8), 2293-2298;
2006. The chemistry is summarized in scheme 16.
##STR00078##
Alternatively, Compounds of formula XIX can be produced from
compounds of formula XXII via nitration reaction. Similar reactions
are well known to those skilled in the art and have been described,
for example in WO-2011049222 or WO-2011049220 (scheme 17).
##STR00079##
The compound of formula XXI can be produced by reacting a compound
of formula XVII with a sulfating agent. Examples of the sulfating
agent to be used in the reaction include sodium sulfide, sodium
sulfide 9-hydrate, and thiourea. The reaction may be conducted in
the presence of a base. Examples of the base to be used in the
reaction include inorganic bases such as potassium carbonate,
cesium carbonate, and tripotassium phosphate; and organic bases,
for example triethylamine. The reaction is generally conducted in
the presence of a solvent. Examples of the solvent to be used in
the reaction include water; alcohols such as methanol and ethanol;
ethers such as THF, ethylene glycol dimethyl ether,
tert-butylmethyl ether, and 1,4-dioxane; aromatic hydrocarbons such
as toluene and xylene; nitriles such as acetonitrile; aprotic polar
solvents such as DMF, NMP, and DMSO; carboxylic acids such as
acetic acid; and mixtures thereof. Similar reactions have been
described in the literature (see, for example: ChemMedChem, 4 (6),
935-938; 2009, Bioorganic & Medicinal Chemistry, 16 (23),
9948-9956; 2008 or Journal of Heterocyclic Chemistry, 38 (5),
1153-1166; 2001). Reduction of the nitro group in compound XXI by
methods known to those skilled in the art, for example with a metal
in acidic medium, for example Fe in acetic acid or hydrochloric
acid. Such reductions of NO.sub.2 groups have been described for
example in Org. Synth.; Coll. Vol. 5: 346, 1973, leads to compounds
of formula XXb. The chemistry is summarized in scheme 16.
Preparation of Quinoxalines derivatives analogues (J1 b): The
compound of formula Ia or Ib wherein R.sub.2, G.sub.1, G.sub.2 and
G.sub.3 are as defined in formula I, L1 and L2 are nitrogen,
L.sub.2 and L.sub.3 are, respectively C--R.sub.10b and
C--R.sub.10c, and Z is a leaving group or X--R.sub.1, can be
produced by reacting a compound of formula XVII (for example,
prepared as describe in scheme 15) with Glyoxal analogues (XXIII)
and transformed in compound of formula I (if Z is a leaving group)
via the conditions described, for example in scheme 3. Such
transformation is well known to those skilled in the art and have
been described, for example in Journal of Heterocyclic Chemistry,
51 (5), 1504-1508; 2014, Synthesis, 45 (11), 1546-1552; 2013 and
cited references. This is illustrated for compounds of formula I in
scheme 19.
##STR00080##
Preparation of benzofuran derivatives analogues (e.g. J27): The
compound of formula I wherein A, R.sub.2, G.sub.1, G.sub.2 and
G.sub.3 are as defined in formula I, L1 is oxygen, L.sub.2 and
L.sub.3 are, respectively C(R.sub.10b).sub.m and
C(R.sub.10c).sub.m, and Z is a leaving group or X--R.sub.1, can be
produced by:
1. reacting compounds of formula XXIV with an allyl analogues such
as compound of formula XXV in presence of a base such as, for
example, potassium carbonate in a solvent such as, for example,
acetone, acetonitrile or dimethylformamide or a mixture of solvent
such as, dimethylformamide and acetone, in presence or not of a
catalyst such as sodium iodine. The formation of the ester XXVI is
analogues to transformation well known by a person skilled in the
art and could be done in conditions described, for example in
Organic Letters, 17 (12), 3118-3121; 2015; Tetrahedron, 2004, 60,
7973-7981 or Protective groups in organic synthesis (third edition,
Theodora W. Greene, Peter G. M. Wuts 1999) p 262.
2. then via Claisen rearrangement of compounds of formula XXVI
under heating conditions. This reaction and the conditions to
realize it are well known to person skilled in the art, see for
example Strategic Applications of Named Reactions in Organic
Synthesis by Kurti, Laszlo; Czako, Barbara; Editors; 2005, page
88.
3. and by cyclisation of compounds of formula XXVII under acidic
condition such as acid formic. Such transformation (Intramolecular
Hydroalkoxylation) is well known to those skilled in the art and
have been described, see for example, Angewandte Chemie,
International Edition, 54 (13), 4014-4017; 2015 and cited
references; ChemCatChem, 5 (11), 3309-3315; 2013; Chemistry--A
European Journal, 16 (11), 3403-3422, S3403/1-S3403/38; 2010 and
cited references; Journal of Organic Chemistry, 76 (22), 9353-9361;
2011.
##STR00081##
Preparation of compounds of formula XXIV could be made, to person
skilled in the art, by the use of protocols described previously in
this patent or with procedures described in WO 2015000715, US
20140018373 (WO 2012086848) or US 20140194290 (WO 2013018928).
For preparing all other compounds of the formula (I) functionalized
according to the definitions of formula III and II, there are a
large number of suitable known standard methods, for example
alkylation, halogenation, acylation, amidation, oximation,
oxidation and reduction, the choice of the preparation methods
which are suitable depending on the properties (reactivity) of the
substituents in the intermediates.
The reactants can be reacted in the presence of a base. Examples of
suitable bases are alkali metal or alkaline earth metal hydroxides,
alkali metal or alkaline earth metal hydrides, alkali metal or
alkaline earth metal amides, alkali metal or alkaline earth metal
alkoxides, alkali metal or alkaline earth metal acetates, alkali
metal or alkaline earth metal carbonates, alkali metal or alkaline
earth metal dialkylamides or alkali metal or alkaline earth metal
alkylsilylamides, alkylamines, alkylenediamines, free or
N-alkylated saturated or unsaturated cycloalkylamines, basic
heterocycles, ammonium hydroxides and carbocyclic amines. Examples
which may be mentioned are sodium hydroxide, sodium hydride, sodium
amide, sodium methoxide, sodium acetate, sodium carbonate,
potassium tert-butoxide, potassium hydroxide, potassium carbonate,
potassium hydride, lithium diisopropylamide, potassium
bis(trimethylsilyl)amide, calcium hydride, triethylamine,
diisopropylethylamine, triethylenediamine, cyclohexylamine,
N-cyclohexyl-N,N-dimethylamine, N,N-diethylaniline, pyridine,
4-(N,N-dimethylamino)pyridine, quinuclidine, N-methylmorpholine,
benzyltrimethylammonium hydroxide and
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).
The reactants can be reacted with each other as such, i.e. without
adding a solvent or diluent. In most cases, however, it is
advantageous to add an inert solvent or diluent or a mixture of
these. If the reaction is carried out in the presence of a base,
bases which are employed in excess, such as triethylamine,
pyridine, N-methylmorpholine or N,N-diethylaniline, may also act as
solvents or diluents.
The reaction is advantageously carried out in a temperature range
from approximately -80.degree. C. to approximately +140.degree. C.,
preferably from approximately -30.degree. C. to approximately
+100.degree. C., in many cases in the range between ambient
temperature and approximately +80.degree. C.
A compound of formula I can be converted in a manner known per se
into another compound of formula I by replacing one or more
substituents of the starting compound of formula I in the customary
manner by (an)other substituent(s) according to the invention.
Depending on the choice of the reaction conditions and starting
materials which are suitable in each case, it is possible, for
example, in one reaction step only to replace one substituent by
another substituent according to the invention, or a plurality of
substituents can be replaced by other substituents according to the
invention in the same reaction step.
Salts of compounds of formula I can be prepared in a manner known
per se. Thus, for example, acid addition salts of compounds of
formula I are obtained by treatment with a suitable acid or a
suitable ion exchanger reagent and salts with bases are obtained by
treatment with a suitable base or with a suitable ion exchanger
reagent.
Salts of compounds of formula I can be converted in the customary
manner into the free compounds I, acid addition salts, for example,
by treatment with a suitable basic compound or with a suitable ion
exchanger reagent and salts with bases, for example, by treatment
with a suitable acid or with a suitable ion exchanger reagent.
Salts of compounds of formula I can be converted in a manner known
per se into other salts of compounds of formula I, acid addition
salts, for example, into other acid addition salts, for example by
treatment of a salt of inorganic acid such as hydrochloride with a
suitable metal salt such as a sodium, barium or silver salt, of an
acid, for example with silver acetate, in a suitable solvent in
which an inorganic salt which forms, for example silver chloride,
is insoluble and thus precipitates from the reaction mixture.
Depending on the procedure or the reaction conditions, the
compounds of formula I, which have salt-forming properties, can be
obtained in free form or in the form of salts.
The compounds of formula I and, where appropriate, the tautomer's
thereof, in each case in free form or in salt form, can be present
in the form of one of the isomers which are possible or as a
mixture of these, for example in the form of pure isomers, such as
antipodes and/or diastereomers, or as isomer mixtures, such as
enantiomer mixtures, for example racemates, diastereomer mixtures
or racemate mixtures, depending on the number, absolute and
relative configuration of asymmetric carbon atoms which occur in
the molecule and/or depending on the configuration of non-aromatic
double bonds which occur in the molecule; the invention relates to
the pure isomers and also to all isomer mixtures which are possible
and is to be understood in each case in this sense hereinabove and
herein below, even when stereochemical details are not mentioned
specifically in each case.
Diastereomer mixtures or racemate mixtures of compounds of formula
I, in free form or in salt form, which can be obtained depending on
which starting materials and procedures have been chosen can be
separated in a known manner into the pure diasteromers or racemates
on the basis of the physicochemical differences of the components,
for example by fractional crystallization, distillation and/or
chromatography.
Enantiomer mixtures, such as racemates, which can be obtained in a
similar manner can be resolved into the optical antipodes by known
methods, for example by recrystallization from an optically active
solvent, by chromatography on chiral adsorbents, for example
high-performance liquid chromatography (HPLC) on acetyl cellulose,
with the aid of suitable microorganisms, by cleavage with specific,
immobilized enzymes, via the formation of inclusion compounds, for
example using chiral crown ethers, where only one enantiomer is
complexed, or by conversion into diastereomeric salts, for example
by reacting a basic end-product racemate with an optically active
acid, such as a carboxylic acid, for example camphor, tartaric or
malic acid, or sulfonic acid, for example camphorsulfonic acid, and
separating the diastereomer mixture which can be obtained in this
manner, for example by fractional crystallization based on their
differing solubilities, to give the diastereomers, from which the
desired enantiomer can be set free by the action of suitable
agents, for example basic agents.
Pure diastereomers or enantiomers can be obtained according to the
invention not only by separating suitable isomer mixtures, but also
by generally known methods of diastereoselective or
enantioselective synthesis, for example by carrying out the process
according to the invention with starting materials of a suitable
stereochemistry.
N-oxides can be prepared by reacting a compound of the formula I
with a suitable oxidizing agent, for example the
H.sub.2O.sub.2/urea adduct in the presence of an acid anhydride,
e.g. trifluoroacetic anhydride. Such oxidations are known from the
literature, for example from J. Med. Chem. 1989, 32, 2561 or WO
2000/15615.
It is advantageous to isolate or synthesize in each case the
biologically more effective isomer, for example enantiomer or
diastereomer, or isomer mixture, for example enantiomer mixture or
diastereomer mixture, if the individual components have a different
biological activity.
The compounds of formula I and, where appropriate, the tautomers
thereof, in each case in free form or in salt form, can, if
appropriate, also be obtained in the form of hydrates and/or
include other solvents, for example those which may have been used
for the crystallization of compounds which are present in solid
form.
The compounds according to the following Tables 1 to 4 below can be
prepared according to the methods described above. The examples
which follow are intended to illustrate the invention and show
preferred compounds of formula I. "Ph" represents the phenyl
group.
Table 1: This table discloses the 128 compounds of the formula
I-1a:
##STR00082##
TABLE-US-00001 TABLE 1 G.sub.3 is N--R.sub.6 Comp. No. X R.sub.1 A
R.sub.2 R.sub.6 L.sub.1 L.sub.2 L.sub.3 L.sub.4 1.001 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH CH CH CH 1.002 SO
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH CH CH CH 1.003
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH CH CH CH
1.004 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH CH CH CH 1.005 SO
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH CH CH CH 1.006 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH CH CH CH 1.007 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 O CH.sub.2 O bond 1.008
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 O CH.sub.2 O
bond- 1.009 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N
N--CH.sub.3 bond 1.010 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 CH N N--CH.sub.3 - bond 1.011 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 CH N--CH.sub.3 N bond 1.012 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N--CH.sub.3 N - bond
1.013 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N N--CH.sub.3
bond 1.014 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N
N--CH.sub.3 bon- d 1.015 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
CH N--CH.sub.3 N bond 1.016 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 CH N--CH.sub.3 N bon- d 1.017 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N CH CH CH 1.018 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N CH CH CH 1.019 S --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N CH CH CH 1.020 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N CH CH CH 1.021 S --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 CH N CH CH 1.022 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 CH N CH CH 1.023 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
CH N CH CH 1.024 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH
N CH CH 1.025 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 N CH Bond 1.026 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N--CH.sub.3 N CH - Bond 1.027 S
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 N CH Bond 1.028
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 N CH
Bon- d 1.029 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
N--CH.sub.3 CH Bond 1.030 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N N--CH.sub.3 CH - Bond 1.031 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N N--CH.sub.3 CH Bond 1.032 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N--CH.sub.3 CH Bon- d
1.033 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N--H CH Bond
1.034 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N--H CH
Bond 1.035 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N--H CH Bond
1.036 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N--H CH
Bond 1.037 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N N--H
bond 1.038 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N
N--H bond 1.039 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N N--H
bond 1.040 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N
N--H bond 1.041 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N S N
bond 1.042 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N S N
bond 1.043 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N S N bond
1.044 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N S N bond
1.045 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N NH N bond 1.046
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N NH N bond
1.047 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N NH N bond 1.048
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N NH N bond 1.049 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N--CH.sub.3 N bond
1.050 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
N--CH.sub.3 N b- ond 1.051 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
N N--CH.sub.3 N bond 1.052 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N N--CH.sub.3 N bond- 1.053 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N N N--CH.sub.3 bond 1.054 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N N--CH.sub.3 b- ond
1.055 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N N--CH.sub.3 bond
1.056 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N
N--CH.sub.3 bond- 1.057 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 N N bond 1.058 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N--CH.sub.3 N N b- ond 1.059 S --CH.sub.2CH.sub.3
N CF.sub.3 CH.sub.3 N--CH.sub.3 N N bond 1.060 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 N N bond- 1.061
S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH C--CF3 CH CH 1.062
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH C--CF.sub.3
CH- CH 1.063 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH
C--CF.sub.3 CH CH 1.064 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 CH C--CF.sub.3 CH CH- 1.065 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 CH C--F CH CH 1.066 SO.sub.2 --CH.sub.2CH.sub.3
C--H CF.sub.3 CH.sub.3 CH C--F CH CH 1.067 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 CH C--F CH CH 1.068 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 CH C--F CH CH 1.069 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N C--H S bond 1.070 SO.sub.2 --CH.sub.2CH.sub.3
C--H CF.sub.3 CH.sub.3 N C--H S bond 1.071 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--H S bond 1.072 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--H S bond 1.073 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N C--CH.sub.3 S bond 1.074 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N C--CH.sub.3 S b- ond
1.075 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CH.sub.3 S bond
1.076 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CH.sub.3
S bond- 1.077 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
C--CF.sub.3 S bond 1.078 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N C--CF.sub.3 S b- ond 1.079 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--CF.sub.3 S bond 1.080 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CF.sub.3 S bond- 1.081
S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--H N bond 1.082
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--H N bond
1.083 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--H N bond 1.084
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--H N bond 1.085
S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--CH.sub.3 N bond
1.086 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S
C--CH.sub.3 N b- ond 1.087 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
S C--CH.sub.3 N bond 1.088 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 S C--CH.sub.3 N bond- 1.089 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 S C--CF.sub.3 N bond 1.090 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--CF.sub.3 N b- ond
1.091 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--CF.sub.3 N bond
1.092 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--CF.sub.3
N bond- 1.093 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H
C--CF.sub.3 N bond 1.094 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N--H C--CF.sub.3 - N bond 1.095 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N--H C--CF.sub.3 N bond 1.096 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--H C--CF.sub.3 N b- ond
1.097 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H C--CH.sub.3
N bond 1.098 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--H C--CH.sub.3 - N bond 1.099 S --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N--H C--CH.sub.3 N bond 1.100 SO.sub.2 --CH.sub.2CH.sub.3
N CF.sub.3 CH.sub.3 N--H C--CH.sub.3 N b- ond 1.101 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H CH N bond 1.102
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H CH N bond
1.103 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--H CH N bond 1.104
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--H CH N bond
1.105 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--CH.sub.3 CH N
bond 1.106 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 CH N - bond 1.107 S --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N--CH.sub.3 CH N bond 1.108 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N--CH.sub.3 CH N bon- d 1.109 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--CH.sub.3 C--CH.sub.3 -
N bond 1.110 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 C--CH- .sub.3 N bond 1.111 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N--CH.sub.3 C--CH.sub.3 N b- ond 1.112 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 C--CH.su- b.3 N
bond 1.113 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--CH.sub.3
C--CF.sub.3 - N bond 1.114 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N--CH.sub.3 C--CF- .sub.3 N bond 1.115 S
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 C--CF.sub.3 N b-
ond 1.116 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
N--CH.sub.3 C--CF.su- b.3 N bond 1.117 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N CH N--CH.sub.3 bond 1.118 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N CH N--CH.sub.3 - bond
1.119 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N CH N--CH.sub.3
bond 1.120 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N CH
N--CH.sub.3 bon- d 1.121 S --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N C--CH.sub.3 N--CH.sub.- 3 bond 1.122 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N C--CH.sub.3 N---
CH.sub.3 bond 1.123 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N
C--CH.sub.3 N--CH.sub.3 b- ond 1.124 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--CH.sub.3 N--CH.- sub.3 bond 1.125 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N C--CF.sub.3 N--CH.sub.-
3 bond 1.126 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
C--CF.sub.3 N--- CH.sub.3 bond 1.127 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--CF.sub.3 N--CH.sub.3 b- ond 1.128 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CF.sub.3 N--CH.- sub.3
bond
and the N-oxides or tautomers of the compounds of Table 1.
Table 2: This table discloses the 128 compounds of the formula
I-1b:
##STR00083##
TABLE-US-00002 TABLE 2 G.sub.3 is N--R.sub.6 Comp. No. X R.sub.1 A
R.sub.2 R.sub.6 L.sub.1 L.sub.2 L.sub.3 L.sub.4 2.001 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH CH CH CH 2.002 SO
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH CH CH CH 2.003
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH CH CH CH
2.004 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH CH CH CH 2.005 SO
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH CH CH CH 2.006 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH CH CH CH 2.007 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 O CH.sub.2 O bond 2.008
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 O CH.sub.2 O
bond- 2.009 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N
N--CH.sub.3 bond 2.010 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 CH N N--CH.sub.3 - bond 2.011 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 CH N--CH.sub.3 N bond 2.012 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N--CH.sub.3 N - bond
2.013 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N N--CH.sub.3
bond 2.014 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N
N--CH.sub.3 bon- d 2.015 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
CH N--CH.sub.3 N bond 2.016 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 CH N--CH.sub.3 N bon- d 2.017 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N CH CH CH 2.018 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N CH CH CH 2.019 S --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N CH CH CH 2.020 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N CH CH CH 2.021 S --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 CH N CH CH 2.022 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 CH N CH CH 2.023 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
CH N CH CH 2.024 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH
N CH CH 2.025 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 N CH bond 2.026 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N--CH.sub.3 N CH - bond 2.027 S
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 N CH bond 2.028
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 N CH
bon- d 2.029 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
N--CH.sub.3 CH bond 2.030 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N N--CH.sub.3 CH - bond 2.031 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N N--CH.sub.3 CH bond 2.032 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N--CH.sub.3 CH bon- d
2.033 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N--H CH bond
2.034 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N--H CH
bond 2.035 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N--H CH bond
2.036 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N--H CH
bond 2.037 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N N--H
bond 2.038 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N
N--H bond 2.039 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N N--H
bond 2.040 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N
N--H bond 2.041 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N S N
bond 2.042 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N S N
bond 2.043 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N S N bond
2.044 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N S N bond
2.045 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N NH N bond 2.046
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N NH N bond
2.047 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N NH N bond 2.048
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N NH N bond 2.049 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N--CH.sub.3 N bond
2.050 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
N--CH.sub.3 N b- ond 2.051 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
N N--CH.sub.3 N bond 2.052 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N N--CH.sub.3 N bond- 2.053 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N N N--CH.sub.3 bond 2.054 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N N--CH.sub.3 b- ond
2.055 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N N--CH.sub.3 bond
2.056 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N
N--CH.sub.3 bond- 2.057 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 N N bond 2.058 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N--CH.sub.3 N N b- ond 2.059 S --CH.sub.2CH.sub.3
N CF.sub.3 CH.sub.3 N--CH.sub.3 N N bond 2.060 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 N N bond- 2.061
S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH C--CF.sub.3 CH CH
2.062 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH
C--CF.sub.3 CH- CH 2.063 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
CH C--CF.sub.3 CH CH 2.064 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 CH C--CF.sub.3 CH CH- 2.065 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 CH C--F CH CH 2.066 SO.sub.2 --CH.sub.2CH.sub.3
C--H CF.sub.3 CH.sub.3 CH C--F CH CH 2.067 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 CH C--F CH CH 2.068 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 CH C--F CH CH 2.069 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N C--H S bond 2.070 SO.sub.2 --CH.sub.2CH.sub.3
C--H CF.sub.3 CH.sub.3 N C--H S bond 2.071 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--H S bond 2.072 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--H S bond 2.073 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N C--CH.sub.3 S bond 2.074 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N C--CH.sub.3 S b- ond
2.075 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CH.sub.3 S bond
2.076 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CH.sub.3
S bond- 2.077 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
C--CF.sub.3 S bond 2.078 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N C--CF.sub.3 S b- ond 2.079 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--CF.sub.3 S bond 2.080 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CF.sub.3 S bond- 2.081
S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--H N bond 2.082
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--H N bond
2.083 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--H N bond 2.084
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--H N bond 2.085
S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--CH.sub.3 N bond
2.086 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S
C--CH.sub.3 N b- ond 2.087 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
S C--CH.sub.3 N bond 2.088 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 S C--CH.sub.3 N bond- 2.089 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 S C--CF.sub.3 N bond 2.090 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--CF.sub.3 N b- ond
2.091 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--CF.sub.3 N bond
2.092 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--CF.sub.3
N bond- 2.093 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H
C--CF.sub.3 N bond 2.094 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N--H C--CF.sub.3 - N bond 2.095 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N--H C--CF.sub.3 N bond 2.096 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--H C--CF.sub.3 N b- ond
2.097 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H C--CH.sub.3
N bond 2.098 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--H C--CH.sub.3 - N bond 2.099 S --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N--H C--CH.sub.3 N bond 2.100 SO.sub.2 --CH.sub.2CH.sub.3
N CF.sub.3 CH.sub.3 N--H C--CH.sub.3 N b- ond 2.101 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H CH N bond 2.102
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H CH N bond
2.103 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--H CH N bond 2.104
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--H CH N bond
2.105 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--CH.sub.3 CH N
bond 2.106 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 CH N - bond 2.107 S --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N--CH.sub.3 CH N bond 2.108 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N--CH.sub.3 CH N bon- d 2.109 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--CH.sub.3 C--CH.sub.3 -
N bond 2.110 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 C--CH- .sub.3 N bond 2.111 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N--CH.sub.3 C--CH.sub.3 N b- ond 2.112 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 C--CH.su- b.3 N
bond 2.113 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--CH.sub.3
C--CF.sub.3 - N bond 2.114 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N--CH.sub.3 C--CF- .sub.3 N bond 2.115 S
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 C--CF.sub.3 N b-
ond 2.116 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
N--CH.sub.3 C--CF.su- b.3 N bond 2.117 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N CH N--CH.sub.3 bond 2.118 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N CH N--CH.sub.3 - bond
2.119 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N CH N--CH.sub.3
bond 2.120 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N CH
N--CH.sub.3 bon- d 2.121 S --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N C--CH.sub.3 N--CH.sub.- 3 bond 2.122 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N C--CH.sub.3 N---
CH.sub.3 bond 2.123 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N
C--CH.sub.3 N--CH.sub.3 b- ond 2.124 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--CH.sub.3 N--CH.- sub.3 bond 2.125 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N C--CF.sub.3 N--CH.sub.-
3 bond 2.126 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
C--CF.sub.3 N--- CH.sub.3 bond 2.127 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--CF.sub.3 N--CH.sub.3 b- ond 2.128 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CF.sub.3 N--CH.- sub.3
bond
and the N-oxides and tautomers of the compounds of Table 2.
Table 3: This table discloses the 128 compounds of the formula
I-1c:
##STR00084##
TABLE-US-00003 TABLE 3 G.sub.3 is N--R.sub.6 Comp. No. X R.sub.1 A
R.sub.2 R.sub.6 L.sub.1 L.sub.2 L.sub.3 L.sub.4 3.001 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH CH CH CH 3.002 SO
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH CH CH CH 3.003
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH CH CH CH
3.004 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH CH CH CH 3.005 SO
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH CH CH CH 3.006 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH CH CH CH 3.007 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 O CH.sub.2 O bond 3.008
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 O CH.sub.2 O
bond- 3.009 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N
N--CH.sub.3 bond 3.010 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 CH N N--CH.sub.3 - bond 3.011 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 CH N--CH.sub.3 N bond 3.012 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N--CH.sub.3 N - bond
3.013 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N N--CH.sub.3
bond 3.014 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N
N--CH.sub.3 bon- d 3.015 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
CH N--CH.sub.3 N bond 3.016 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 CH N--CH.sub.3 N bon- d 3.017 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N CH CH CH 3.018 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N CH CH CH 3.019 S --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N CH CH CH 3.020 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N CH CH CH 3.021 S --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 CH N CH CH 3.022 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 CH N CH CH 3.023 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
CH N CH CH 3.024 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH
N CH CH 3.025 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 N CH bond 3.026 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N--CH.sub.3 N CH - bond 3.027 S
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 N CH bond 3.028
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 N CH
bon- d 3.029 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
N--CH.sub.3 CH bond 3.030 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N N--CH.sub.3 CH - bond 3.031 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N N--CH.sub.3 CH bond 3.032 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N--CH.sub.3 CH bon- d
3.033 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N--H CH bond
3.034 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N--H CH
bond 3.035 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N--H CH bond
3.036 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N--H CH
bond 3.037 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N N--H
bond 3.038 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N
N--H bond 3.039 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N N--H
bond 3.040 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N
N--H bond 3.041 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N S N
bond 3.042 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N S N
bond 3.043 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N S N bond
3.044 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N S N bond
3.045 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N NH N bond 3.046
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N NH N bond
3.047 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N NH N bond 3.048
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N NH N bond 3.049 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N--CH.sub.3 N bond
3.050 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
N--CH.sub.3 N b- ond 3.051 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
N N--CH.sub.3 N bond 3.052 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N N--CH.sub.3 N bond- 3.053 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N N N--CH.sub.3 bond 3.054 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N N--CH.sub.3 b- ond
3.055 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N N--CH.sub.3 bond
3.056 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N
N--CH.sub.3 bond- 3.057 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 N N bond 3.058 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N--CH.sub.3 N N b- ond 3.059 S --CH.sub.2CH.sub.3
N CF.sub.3 CH.sub.3 N--CH.sub.3 N N bond 3.060 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 N N bond- 3.061
S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH C--CF.sub.3 CH CH
3.062 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH
C--CF.sub.3 CH- CH 3.063 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
CH C--CF.sub.3 CH CH 3.064 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 CH C--CF.sub.3 CH CH- 3.065 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 CH C--F CH CH 3.066 SO.sub.2 --CH.sub.2CH.sub.3
C--H CF.sub.3 CH.sub.3 CH C--F CH CH 3.067 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 CH C--F CH CH 3.068 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 CH C--F CH CH 3.069 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N C--H S bond 3.070 SO.sub.2 --CH.sub.2CH.sub.3
C--H CF.sub.3 CH.sub.3 N C--H S bond 3.071 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--H S bond 3.072 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--H S bond 3.073 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N C--CH.sub.3 S bond 3.074 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N C--CH.sub.3 S b- ond
3.075 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CH.sub.3 S bond
3.076 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CH.sub.3
S bond- 3.077 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
C--CF.sub.3 S bond 3.078 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N C--CF.sub.3 S b- ond 3.079 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--CF.sub.3 S bond 3.080 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CF.sub.3 S bond- 3.081
S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--H N bond 3.082
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--H N bond
3.083 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--H N bond 3.084
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--H N bond 3.085
S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--CH.sub.3 N bond
3.086 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S
C--CH.sub.3 N b- ond 3.087 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
S C--CH.sub.3 N bond 3.088 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 S C--CH.sub.3 N bond- 3.089 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 S C--CF.sub.3 N bond 3.090 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--CF.sub.3 N b- ond
3.091 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--CF.sub.3 N bond
3.092 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--CF.sub.3
N bond- 3.093 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H
C--CF.sub.3 N bond 3.094 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N--H C--CF.sub.3 - N bond 3.095 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N--H C--CF.sub.3 N bond 3.096 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--H C--CF.sub.3 N b- ond
3.097 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H C--CH.sub.3
N bond 3.098 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--H C--CH.sub.3 - N bond 3.099 S --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N--H C--CH.sub.3 N bond 3.100 SO.sub.2 --CH.sub.2CH.sub.3
N CF.sub.3 CH.sub.3 N--H C--CH.sub.3 N b- ond 3.101 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H CH N bond 3.102
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H CH N bond
3.103 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--H CH N bond 3.104
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--H CH N bond
3.105 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--CH.sub.3 CH N
bond 3.106 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 CH N - bond 3.107 S --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N--CH.sub.3 CH N bond 3.108 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N--CH.sub.3 CH N bon- d 3.109 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--CH.sub.3 C--CH.sub.3 -
N bond 3.110 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 C--CH- .sub.3 N bond 3.111 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N--CH.sub.3 C--CH.sub.3 N b- ond 3.112 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 C--CH.su- b.3 N
bond 3.113 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--CH.sub.3
C--CF.sub.3 - N bond 3.114 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N--CH.sub.3 C--CF- .sub.3 N bond 3.115 S
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 C--CF.sub.3 N b-
ond 3.116 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
N--CH.sub.3 C--CF.su- b.3 N bond 3.117 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N CH N--CH.sub.3 bond 3.118 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N CH N--CH.sub.3 - bond
3.119 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N CH N--CH.sub.3
bond 3.120 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N CH
N--CH.sub.3 bon- d 3.121 S --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N C--CH.sub.3 N--CH.sub.- 3 bond 3.122 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N C--CH.sub.3 N---
CH.sub.3 bond 3.123 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N
C--CH.sub.3 N--CH.sub.3 b- ond 3.124 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--CH.sub.3 N--CH.- sub.3 bond 3.125 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N C--CF.sub.3 N--CH.sub.-
3 bond 3.126 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
C--CF.sub.3 N--- CH.sub.3 bond 3.127 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--CF.sub.3 N--CH.sub.3 b- ond 3.128 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CF.sub.3 N--CH.- sub.3
bond
and the N-oxides and tautomers of the compounds of Table 3.
Table 4: This table discloses the 128 compounds of the formula
I-1d:
##STR00085##
TABLE-US-00004 TABLE 4 G.sub.3 is N--R.sub.6 Comp. No. X R.sub.1 A
R.sub.2 R.sub.6 L.sub.1 L.sub.2 L.sub.3 L.sub.4 4.001 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH CH CH CH 4.002 SO
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH CH CH CH 4.003
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH CH CH CH
4.004 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH CH CH CH 4.005 SO
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH CH CH CH 4.006 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH CH CH CH 4.007 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 O CH.sub.2 O bond 4.008
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 O CH.sub.2 O
bond- 4.009 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N
N--CH.sub.3 bond 4.010 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 CH N N--CH.sub.3 - bond 4.011 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 CH N--CH.sub.3 N bond 4.012 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N--CH.sub.3 N - bond
4.013 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N N--CH.sub.3
bond 4.014 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N
N--CH.sub.3 bon- d 4.015 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
CH N--CH.sub.3 N bond 4.016 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 CH N--CH.sub.3 N bon- d 4.017 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N CH CH CH 4.018 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N CH CH CH 4.019 S --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N CH CH CH 4.020 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N CH CH CH 4.021 S --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 CH N CH CH 4.022 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 CH N CH CH 4.023 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
CH N CH CH 4.024 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH
N CH CH 4.025 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 N CH bond 4.026 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N--CH.sub.3 N CH - bond 4.027 S
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 N CH bond 4.028
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 N CH
bon- d 4.029 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
N--CH.sub.3 CH bond 4.030 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N N--CH.sub.3 CH - bond 4.031 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N N--CH.sub.3 CH bond 4.032 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N--CH.sub.3 CH bon- d
4.033 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N--H CH bond
4.034 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N--H CH
bond 4.035 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N--H CH bond
4.036 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N--H CH
Bond 4.037 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N N--H
bond 4.038 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH N
N--H bond 4.039 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N N--H
bond 4.040 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 CH N
N--H bond 4.041 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N S N
bond 4.042 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N S N
bond 4.043 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N S N bond
4.044 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N S N bond
4.045 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N NH N bond 4.046
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N NH N bond
4.047 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N NH N bond 4.048
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N NH N bond 4.049 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N--CH.sub.3 N bond
4.050 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
N--CH.sub.3 N b- ond 4.051 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
N N--CH.sub.3 N bond 4.052 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N N--CH.sub.3 N bond- 4.053 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N N N--CH.sub.3 bond 4.054 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N N N--CH.sub.3 b- ond
4.055 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N N--CH.sub.3 bond
4.056 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N N
N--CH.sub.3 bond- 4.057 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 N N bond 4.058 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N--CH.sub.3 N N b- ond 4.059 S --CH.sub.2CH.sub.3
N CF.sub.3 CH.sub.3 N--CH.sub.3 N N bond 4.060 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 N N bond- 4.061
S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH C--CF.sub.3 CH CH
4.062 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 CH
C--CF.sub.3 CH- CH 4.063 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
CH C--CF.sub.3 CH CH 4.064 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 CH C--CF.sub.3 CH CH- 4.065 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 CH C--F CH CH 4.066 SO.sub.2 --CH.sub.2CH.sub.3
C--H CF.sub.3 CH.sub.3 CH C--F CH CH 4.067 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 CH C--F CH CH 4.068 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 CH C--F CH CH 4.069 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N C--H S bond 4.070 SO.sub.2 --CH.sub.2CH.sub.3
C--H CF.sub.3 CH.sub.3 N C--H S bond 4.071 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--H S bond 4.072 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--H S bond 4.073 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N C--CH.sub.3 S bond 4.074 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N C--CH.sub.3 S b- ond
4.075 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CH.sub.3 S bond
4.076 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CH.sub.3
S bond- 4.077 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
C--CF.sub.3 S bond 4.078 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N C--CF.sub.3 S b- ond 4.079 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--CF.sub.3 S bond 4.080 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CF.sub.3 S bond- 4.081
S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--H N bond 4.082
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--H N bond
4.083 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--H N bond 4.084
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--H N bond 4.085
S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--CH.sub.3 N bond
4.086 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S
C--CH.sub.3 N b- ond 4.087 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
S C--CH.sub.3 N bond 4.088 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 S C--CH.sub.3 N bond- 4.089 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 S C--CF.sub.3 N bond 4.090 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 S C--CF.sub.3 N b- ond
4.091 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--CF.sub.3 N bond
4.092 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 S C--CF.sub.3
N bond- 4.093 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H
C--CF.sub.3 N bond 4.094 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N--H C--CF.sub.3 - N bond 4.095 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N--H C--CF.sub.3 N bond 4.096 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--H C--CF.sub.3 N b- ond
4.097 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H C--CH.sub.3
N bond 4.098 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--H C--CH.sub.3 - N bond 4.099 S --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N--H C--CH.sub.3 N bond 4.100 SO.sub.2 --CH.sub.2CH.sub.3
N CF.sub.3 CH.sub.3 N--H C--CH.sub.3 N b- ond 4.101 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H CH N bond 4.102
SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--H CH N bond
4.103 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--H CH N bond 4.104
SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--H CH N bond
4.105 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--CH.sub.3 CH N
bond 4.106 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 CH N - bond 4.107 S --CH.sub.2CH.sub.3 N CF.sub.3
CH.sub.3 N--CH.sub.3 CH N bond 4.108 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N--CH.sub.3 CH N bon- d 4.109 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--CH.sub.3 C--CH.sub.3 -
N bond 4.110 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3
N--CH.sub.3 C--CH- .sub.3 N bond 4.111 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N--CH.sub.3 C--CH.sub.3 N b- ond 4.112 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 C--CH.su- b.3 N
bond 4.113 S --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N--CH.sub.3
C--CF.sub.3 - N bond 4.114 SO.sub.2 --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N--CH.sub.3 C--CF- .sub.3 N bond 4.115 S
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N--CH.sub.3 C--CF.sub.3 N b-
ond 4.116 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3
N--CH.sub.3 C--CF.su- b.3 N bond 4.117 S --CH.sub.2CH.sub.3 C--H
CF.sub.3 CH.sub.3 N CH N--CH.sub.3 bond 4.118 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N CH N--CH.sub.3 - bond
4.119 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N CH N--CH.sub.3
bond 4.120 SO.sub.2 --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N CH
N--CH.sub.3 bon- d 4.121 S --CH.sub.2CH.sub.3 C--H CF.sub.3
CH.sub.3 N C--CH.sub.3 N--CH.sub.- 3 bond 4.122 SO.sub.2
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N C--CH.sub.3 N---
CH.sub.3 bond 4.123 S --CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N
C--CH.sub.3 N--CH.sub.3 b- ond 4.124 SO.sub.2 --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--CH.sub.3 N--CH.- sub.3 bond 4.125 S
--CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N C--CF.sub.3 N--CH.sub.-
3 bond 4.126 SO.sub.2 --CH.sub.2CH.sub.3 C--H CF.sub.3 CH.sub.3 N
C--CF.sub.3 N--- CH.sub.3 bond 4.127 S --CH.sub.2CH.sub.3 N
CF.sub.3 CH.sub.3 N C--CF.sub.3 N--CH.sub.3 b- ond 4.128 SO.sub.2
--CH.sub.2CH.sub.3 N CF.sub.3 CH.sub.3 N C--CF.sub.3 N--CH.- sub.3
bond
and the N-oxides and tautomers of the compounds of Table 4.
The compounds of formula I according to the invention are
preventively and/or curatively valuable active ingredients in the
field of pest control, even at low rates of application, which have
a very favorable biocidal spectrum and are well tolerated by
warm-blooded species, fish and plants. The active ingredients
according to the invention act against all or individual
developmental stages of normally sensitive, but also resistant,
animal pests, such as insects or representatives of the order
Acarina. The insecticidal or acaricidal activity of the active
ingredients according to the invention can manifest itself
directly, i. e. in destruction of the pests, which takes place
either immediately or only after some time has elapsed, for example
during ecdysis, or indirectly, for example in a reduced oviposition
and/or hatching rate.
Examples of the abovementioned animal pests are:
from the order Acarina, for example,
Acalitus spp, Aculus spp, Acaricalus spp, Aceria spp, Acarus siro,
Amblyomma spp., Argas spp., Boophilus spp., Brevipalpus spp.,
Bryobia spp, Calipitrimerus spp., Chorioptes spp., Dermanyssus
gallinae, Dermatophagoides spp, Eotetranychus spp, Eriophyes spp.,
Hemitarsonemus spp, Hyalomma spp., Ixodes spp., Olygonychus spp,
Ornithodoros spp., Polyphagotarsone latus, Panonychus spp.,
Phyllocoptruta oleivora, Phytonemus spp, Polyphagotarsonemus spp,
Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes
spp., Steneotarsonemus spp, Tarsonemus spp. and Tetranychus
spp.;
from the order Anoplura, for example,
Haematopinus spp., Linognathus spp., Pediculus spp., Pemphigus spp.
and Phylloxera spp.; from the order Coleoptera, for example,
Agriotes spp., Amphimallon majale, Anomala orientalis, Anthonomus
spp., Aphodius spp, Astylus atromaculatus, Ataenius spp, Atomaria
linearis, Chaetocnema tibialis, Cerotoma spp, Conoderus spp,
Cosmopolites spp., Cotinis nitida, Curculio spp., Cyclocephala spp,
Dermestes spp., Diabrotica spp., Diloboderus abderus, Epilachna
spp., Eremnus spp., Heteronychus arator, Hypothenemus hampei,
Lagria vilosa, Leptinotarsa decemLineata, Lissorhoptrus spp.,
Liogenys spp, Maecolaspis spp, Maladera castanea, Megascelis spp,
Melighetes aeneus, Melolontha spp., Myochrous armatus, Orycaephilus
spp., Otiorhynchus spp., Phyllophaga spp, Phlyctinus spp., Popillia
spp., Psylliodes spp., Rhyssomatus aubtilis, Rhizopertha spp.,
Scarabeidae, Sitophilus spp., Sitotroga spp., Somaticus spp,
Sphenophorus spp, Sternechus subsignatus, Tenebrio spp., Tribolium
spp. and Trogoderma spp.;
from the order Diptera, for example,
Aedes spp., Anopheles spp, Antherigona soccata, Bactrocea oleae,
Bibio hortulanus, Bradysia spp, Calliphora erythrocephala,
Ceratitis spp., Chrysomyia spp., Culex spp., Cuterebra spp., Dacus
spp., Delia spp, Drosophila melanogaster, Fannia spp., Gastrophilus
spp., Geomyza tripunctata, Glossina spp., Hypoderma spp.,
Hyppobosca spp., Liriomyza spp., Lucilia spp., Melanagromyza spp.,
Musca spp., Oestrus spp., Orseolia spp., Oscinella frit, Pegomyia
hyoscyami, Phorbia spp., Rhagoletis spp, Rivelia quadrifasciata,
Scatella spp, Sciara spp., Stomoxys spp., Tabanus spp., Tannia spp.
and Tipula spp.;
from the order Hemiptera, for example,
Acanthocoris scabrator, Acrosternum spp, Adelphocoris lineolatus,
Amblypelta nitida, Bathycoelia thalassina, Blissus spp, Cimexspp.,
Clavigralla tomentosicollis, Creontiades spp, Distantiella
theobroma, Dichelops furcatus, Dysdercus spp., Edessa spp,
Euchistus spp., Eurydema pulchrum, Eurygaster spp., Halyomorpha
halys, Horcias nobilellus, Leptocorisa spp., Lygus spp, Margarodes
spp, Murgantia histrionic, Neomegalotomus spp, Nesidiocoris tenuis,
Nezara spp., Nysius simulans, Oebalus insularis, Piesma spp.,
Piezodorus spp, Rhodnius spp., Sahlbergella singularis, Scaptocoris
castanea, Scotino-phara spp., Thyanta spp, Triatoma spp., Vatiga
illudens;
Acyrthosium pisum, Adalges spp, Agalliana ensigera, Agonoscena
targionii, Aleurodicus spp, Aleurocanthus spp, Aleurolobus
barodensis, Aleurothrixus floccosus, Aleyrodes brassicae, Amarasca
biguttula, Amritodus atkinsoni, Aonidiella spp., Aphididae, Aphis
spp., Aspidiotus spp., Aulacorthum solani, Bactericera cockerelli,
Bemisia spp, Brachycaudus spp, Brevicoryne brassicae, Cacopsylla
spp, Cavariella aegopodii Scop., Ceroplaster spp., Chrysomphalus
aonidium, Chrysomphalus dictyospermi, Cicadella spp, Cofana
spectra, Cryptomyzus spp, Cicadulina spp, Coccus hesperidum,
Dalbulus maidis, Dialeurodes spp, Diaphorina citri, Diuraphis
noxia, Dysaphis spp, Empoasca spp., Eriosoma larigerum,
Erythroneura spp., Gascardia spp., Glycaspis brimblecombei,
Hyadaphis pseudobrassicae, Hyalopterus spp, Hyperomyzus pallidus,
Idioscopus clypealis, Jacobiasca lybica, Laodelphax spp., Lecanium
corni, Lepidosaphes spp., Lopaphis erysimi, Lyogenys maidis,
Macrosiphum spp., Mahanarva spp, Metcalfa pruinosa, Metopolophium
dirhodum, Myndus crudus, Myzus spp., Neotoxoptera sp, Nephotettix
spp., Nilaparvata spp., Nippolachnus piri Mats, Odonaspis ruthae,
Oregma lanigera Zehnter, Parabemisia myricae, Paratrioza
cockerelli, Parlatoria spp., Pemphigus spp., Peregrinus maidis,
Perkinsiella spp, Phorodon humuli, Phylloxera spp, Planococcus
spp., Pseudaulacaspis spp., Pseudococcus spp., Pseudatomoscelis
seriatus, Psylla spp., Pulvinaria aethiopica, Quadraspidiotus spp.,
Quesada gigas, Recilia dorsalis, Rhopalosiphum spp., Saissetia
spp., Scaphoideus spp., Schizaphis spp., Sitobion spp., Sogatella
furcifera, Spissistilus festinus, Tarophagus Proserpina, Toxoptera
spp, Trialeurodes spp, Tridiscus sporoboli, Trionymus spp, Trioza
erytreae, Unaspis citri, Zygina flammigera, Zyginidia
scutellaris;
from the order Hymenoptera, for example,
Acromyrmex, Arge spp, Atta spp., Cephus spp., Diprion spp.,
Diprionidae, Gilpinia polytoma, Hoplocampa spp., Lasius spp.,
Monomorium pharaonis, Neodiprion spp., Pogonomyrmex spp, Slenopsis
invicta, Solenopsis spp. and Vespa spp.;
from the order Isoptera, for example,
Coptotermes spp, Corniternes cumulans, Incisitermes spp,
Macrotermes spp, Mastotermes spp, Microtermes spp, Reticulitermes
spp.; Solenopsis geminate
from the order Lepidoptera, for example,
Acleris spp., Adoxophyes spp., Aegeria spp., Agrotis spp., Alabama
argillaceae, Amylois spp., Anticarsia gemmatalis, Archips spp.,
Argyresthia spp, Argyrotaenia spp., Autographa spp., Bucculatrix
thurberiella, Busseola fusca, Cadra cautella, Carposina
nipponensis, Chilo spp., Choristoneura spp., Chrysoteuchia
topiaria, Clysia ambiguella, Cnaphalocrocis spp., Cnephasia spp.,
Cochylis spp., Coleophora spp., Colias lesbia, Cosmophila flava,
Crambus spp, Crocidolomia binotalis, Cryptophlebia leucotreta,
Cydalima perspectalis, Cydia spp., Diaphania perspectalis, Diatraea
spp., Diparopsis castanea, Earias spp., Eldana saccharina, Ephestia
spp., Epinotia spp, Estigmene acrea, Etiella zinckinella, Eucosma
spp., Eupoecilia ambiguella, Euproctis spp., Euxoa spp., Feltia
jaculiferia, Grapholita spp., Hedya nubiferana, Heliothis spp.,
Hellula undalis, Herpetogramma spp, Hyphantria cunea, Keiferia
lycopersicella, Lasmopalpus lignosellus, Leucoptera scitella,
Lithocollethis spp., Lobesia botrana, Loxostege bifidalis,
Lymantria spp., Lyonetia spp., Malacosoma spp., Mamestra brassicae,
Manduca sexta, Mythimna spp, Noctua spp, Operophtera spp., Orniodes
indica, Ostrinia nubilalis, Pammene spp., Pandemis spp., Panolis
flammea, Papaipema nebris, Pectinophora gossypiela, Perileucoptera
coffeella, Pseudaletia unipuncta, Phthorimaea operculella, Pieris
rapae, Pieris spp., Plutella xylostella, Prays spp., Pseudoplusia
spp, Rachiplusia nu, Richia albicosta, Scirpophaga spp., Sesamia
spp., Sparganothis spp., Spodoptera spp., Sylepta derogate,
Synanthedon spp., Thaumetopoea spp., Tortrix spp., Trichoplusia ni,
Tuta absoluta, and Yponomeuta spp.;
from the order Mallophaga, for example,
Damalinea spp. and Trichodectes spp.;
from the order Orthoptera, for example,
Blatta spp., Blattella spp., Gryllotalpa spp., Leucophaea maderae,
Locusta spp., Neocurtilla hexadactyla, Periplaneta spp.,
Scapteriscus spp, and Schistocerca spp.;
from the order Psocoptera, for example,
Liposcelis spp.;
from the order Siphonaptera, for example,
Ceratophyllus spp., Ctenocephalides spp. and Xenopsylla
cheopis;
from the order Thysanoptera, for example,
Calliothrips phaseoli, Frankliniella spp., Heliothrips spp,
Hercinothrips spp., Parthenothrips spp, Scirtothrips aurantii,
Sericothrips variabilis, Taeniothrips spp., Thrips spp;
from the order Thysanura, for example, Lepisma saccharina.
The active ingredients according to the invention can be used for
controlling, i. e. containing or destroying, pests of the
abovementioned type which occur in particular on plants, especially
on useful plants and ornamentals in agriculture, in horticulture
and in forests, or on organs, such as fruits, flowers, foliage,
stalks, tubers or roots, of such plants, and in some cases even
plant organs which are formed at a later point in time remain
protected against these pests.
Suitable target crops are, in particular, cereals, such as wheat,
barley, rye, oats, rice, maize or sorghum; beet, such as sugar or
fodder beet; fruit, for example pomaceous fruit, stone fruit or
soft fruit, such as apples, pears, plums, peaches, almonds,
cherries or berries, for example strawberries, raspberries or
blackberries; leguminous crops, such as beans, lentils, peas or
soya; oil crops, such as oilseed rape, mustard, poppies, olives,
sunflowers, coconut, castor, cocoa or ground nuts; cucurbits, such
as pumpkins, cucumbers or melons; fibre plants, such as cotton,
flax, hemp or jute; citrus fruit, such as oranges, lemons,
grapefruit or tangerines; vegetables, such as spinach, lettuce,
asparagus, cabbages, carrots, onions, tomatoes, potatoes or bell
peppers; Lauraceae, such as avocado, Cinnamonium or camphor; and
also tobacco, nuts, coffee, eggplants, sugarcane, tea, pepper,
grapevines, hops, the plantain family and latex plants.
The compositions and/or methods of the present invention may be
also used on any ornamental and/or vegetable crops, including
flowers, shrubs, broad-leaved trees and evergreens.
For example the invention may be used on any of the following
ornamental species: Ageratum spp., Alonsoa spp., Anemone spp.,
Anisodontea capsenisis, Anthemis spp., Antirrhinum spp., Aster
spp., Begonia spp. (e.g. B. elatior, B. semperflorens, B.
tubereux), Bougainvillea spp., Brachycome spp., Brassica spp.
(ornamental), Calceolaria spp., Capsicum annuum, Catharanthus
roseus, Canna spp., Centaurea spp., Chrysanthemum spp., Cineraria
spp. (C. maritime), Coreopsis spp., Crassula coccinea, Cuphea
ignea, Dahlia spp., Delphinium spp., Dicentra spectabilis,
Dorotheantus spp., Eustoma grandiflorum, Forsythia spp., Fuchsia
spp., Geranium gnaphalium, Gerbera spp., Gomphrena globosa,
Heliotropium spp., Helianthus spp., Hibiscus spp., Hortensia spp.,
Hydrangea spp., Hypoestes phyllostachya, Impatiens spp. (I.
Walleriana), Iresines spp., Kalanchoe spp., Lantana camara,
Lavatera trimestris, Leonotis leonurus, Lilium spp.,
Mesembryanthemum spp., Mimulus spp., Monarda spp., Nemesia spp.,
Tagetes spp., Dianthus spp. (carnation), Canna spp., Oxalis spp.,
Bellis spp., Pelargonium spp. (P. peltatum, P. Zonale), Viola spp.
(pansy), Petunia spp., Phlox spp., Plecthranthus spp., Poinsettia
spp., Parthenocissus spp. (P. quinquefolia, P. tricuspidata),
Primula spp., Ranunculus spp., Rhododendron spp., Rosa spp. (rose),
Rudbeckia spp., Saintpaulia spp., Salvia spp., Scaevola aemola,
Schizanthus wisetonensis, Sedum spp., Solanum spp., Surfinia spp.,
Tagetes spp., Nicotinia spp., Verbena spp., Zinnia spp. and other
bedding plants.
For example the invention may be used on any of the following
vegetable species: Allium spp. (A. sativum, A. cepa, A. oschaninii,
A. Porrum, A. ascalonicum, A. fistulosum), Anthriscus cerefolium,
Apium graveolus, Asparagus officinalis, Beta vulgarus, Brassica
spp. (B. Oleracea, B. Pekinensis, B. rapa), Capsicum annuum, Cicer
arietinum, Cichorium endivia, Cichorum spp. (C. intybus, C.
endivia), Citrillus lanatus, Cucumis spp. (C. sativus, C. melo),
Cucurbita spp. (C. pepo, C. maxima), Cyanara spp. (C. scolymus, C.
cardunculus), Daucus carota, Foeniculum vulgare, Hypericum spp.,
Lactuca sativa, Lycopersicon spp. (L. esculentum, L. lycopersicum),
Mentha spp., Ocimum basilicum, Petroselinum crispum, Phaseolus spp.
(P. vulgaris, P. coccineus), Pisum sativum, Raphanus sativus, Rheum
rhaponticum, Rosemarinus spp., Salvia spp., Scorzonera hispanica,
Solanum melongena, Spinacea oleracea, Valerianella spp. (V.
locusta, V. eriocarpa) and Vicia faba.
Preferred ornamental species include African violet, Begonia,
Dahlia, Gerbera, Hydrangea, Verbena, Rosa, Kalanchoe, Poinsettia,
Aster, Centaurea, Coreopsis, Delphinium, Monarda, Phlox, Rudbeckia,
Sedum, Petunia, Viola, Impatiens, Geranium, Chrysanthemum,
Ranunculus, Fuchsia, Salvia, Hortensia, rosemary, sage, St.
Johnswort, mint, sweet pepper, tomato and cucumber.
The active ingredients according to the invention are especially
suitable for controlling Aphis craccivora, Diabrotica balteata,
Heliothis virescens, Myzus persicae, Plutella xylostella and
Spodoptera littoralis in cotton, vegetable, maize, rice and soya
crops. The active ingredients according to the invention are
further especially suitable for controlling Mamestra (preferably in
vegetables), Cydia pomonella (preferably in apples), Empoasca
(preferably in vegetables, vineyards), Leptinotarsa (preferably in
potatos) and Chilo supressalis (preferably in rice).
In a further aspect, the invention may also relate to a method of
controlling damage to plant and parts thereof by plant parasitic
nematodes (Endoparasitic-, Semiendoparasitic- and Ectoparasitic
nematodes), especially plant parasitic nematodes such as root knot
nematodes, Meloidogyne hapla, Meloidogyne incognita, Meloidogyne
javanica, Meloidogyne arenaria and other Meloidogyne species;
cyst-forming nematodes, Globodera rostochiensis and other Globodera
species; Heterodera avenae, Heterodera glycines, Heterodera
schachtii, Heterodera trifolii, and other Heterodera species; Seed
gall nematodes, Anguina species; Stem and foliar nematodes,
Aphelenchoides species; Sting nematodes, Belonolaimus longicaudatus
and other Belonolaimus species; Pine nematodes, Bursaphelenchus
xylophilus and other Bursaphelenchus species; Ring nematodes,
Criconema species, Criconemella species, Criconemoides species,
Mesocriconema species; Stem and bulb nematodes, Ditylenchus
destructor, Ditylenchus dipsaci and other Ditylenchus species; Awl
nematodes, Dolichodorus species; Spiral nematodes, Heliocotylenchus
multicinctus and other Helicotylenchus species; Sheath and
sheathoid nematodes, Hemicycliophora species and Hemicriconemoides
species; Hirshmanniella species; Lance nematodes, Hoploaimus
species; false rootknot nematodes, Nacobbus species; Needle
nematodes, Longidorus elongatus and other Longidorus species; Pin
nematodes, Pratylenchus species; Lesion nematodes, Pratylenchus
neglectus, Pratylenchus penetrans, Pratylenchus curvitatus,
Pratylenchus goodeyi and other Pratylenchus species; Burrowing
nematodes, Radopholus similis and other Radopholus species;
Reniform nematodes, Rotylenchus robustus, Rotylenchus reniformis
and other Rotylenchus species; Scutellonema species; Stubby root
nematodes, Trichodorus primitivus and other Trichodorus species,
Paratrichodorus species; Stunt nematodes, Tylenchorhynchus
claytoni, Tylenchorhynchus dubius and other Tylenchorhynchus
species; Citrus nematodes, Tylenchulus species; Dagger nematodes,
Xiphinema species; and other plant parasitic nematode species, such
as Subanguina spp., Hypsoperine spp., Macroposthonia spp., Melinius
spp., Punctodera spp., and Quinisulcius spp.
The compounds of the invention may also have activity against the
molluscs. Examples of which include, for example, Ampullariidae;
Arion (A. ater, A. circumscriptus, A. hortensis, A. rufus);
Bradybaenidae (Bradybaena fruticum); Cepaea (C. hortensis, C.
Nemoralis); ochlodina; Deroceras (D. agrestis, D. empiricorum, D.
laeve, D. reticulatum); Discus (D. rotundatus); Euomphalia; Galba
(G. trunculata); Helicelia (H. itala, H. obvia); Helicidae
Helicigona arbustorum); Helicodiscus; Helix (H. aperta); Limax (L.
cinereoniger, L. flavus, L. marginatus, L. maximus, L. tenellus);
Lymnaea; Milax (M. gagates, M. marginatus, M. sowerbyi); Opeas;
Pomacea (P. canaticulata); Vallonia and Zanitoides.
The term "crops" is to be understood as including also crop plants
which have been so transformed by the use of recombinant DNA
techniques that they are capable of synthesising one or more
selectively acting toxins, such as are known, for example, from
toxin-producing bacteria, especially those of the genus
Bacillus.
Toxins that can be expressed by such transgenic plants include, for
example, insecticidal proteins, for example insecticidal proteins
from Bacillus cereus or Bacillus popilliae; or insecticidal
proteins from Bacillus thuringiensis, such as .delta.-endotoxins,
e.g. Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or
Cry9C, or vegetative insecticidal proteins (Vip), e.g. Vip1, Vip2,
Vip3 or Vip3A; or insecticidal proteins of bacteria colonising
nematodes, for example Photorhabdus spp. or Xenorhabdus spp., such
as Photorhabdus luminescens, Xenorhabdus nematophilus; toxins
produced by animals, such as scorpion toxins, arachnid toxins, wasp
toxins and other insect-specific neurotoxins; toxins produced by
fungi, such as Streptomycetes toxins, plant lectins, such as pea
lectins, barley lectins or snowdrop lectins; agglutinins;
proteinase inhibitors, such as trypsin inhibitors, serine protease
inhibitors, patatin, cystatin, papain inhibitors;
ribosome-inactivating proteins (RIP), such as ricin, maize-RIP,
abrin, luffin, saporin or bryodin; steroid metabolism enzymes, such
as 3-hydroxysteroidoxidase, ecdysteroid-UDP-glycosyl-transferase,
cholesterol oxidases, ecdysone inhibitors, HMG-COA-reductase, ion
channel blockers, such as blockers of sodium or calcium channels,
juvenile hormone esterase, diuretic hormone receptors, stilbene
synthase, bibenzyl synthase, chitinases and glucanases.
In the context of the present invention there are to be understood
by 6-endotoxins, for example Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2,
Cry2Ab, Cry3A, Cry3Bb1 or Cry9C, or vegetative insecticidal
proteins (Vip), for example Vip1, Vip2, Vip3 or Vip3A, expressly
also hybrid toxins, truncated toxins and modified toxins.
Hybrid toxins are produced recombinantly by a new combination of
different domains of those proteins (see, for example, WO
02/15701). Truncated toxins, for example a truncated Cry1Ab, are
known. In the case of modified toxins, one or more amino acids of
the naturally occurring toxin are replaced. In such amino acid
replacements, preferably non-naturally present protease recognition
sequences are inserted into the toxin, such as, for example, in the
case of Cry3A055, a cathepsin-G-recognition sequence is inserted
into a Cry3A toxin (see WO 03/018810).
Examples of such toxins or transgenic plants capable of
synthesising such toxins are disclosed, for example, in EP-A-0 374
753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878 and WO
03/052073.
The processes for the preparation of such transgenic plants are
generally known to the person skilled in the art and are described,
for example, in the publications mentioned above. Cry1-type
deoxyribonucleic acids and their preparation are known, for
example, from WO 95/34656, EP-A-0 367 474, EP-A-0 401 979 and WO
90/13651.
The toxin contained in the transgenic plants imparts to the plants
tolerance to harmful insects. Such insects can occur in any
taxonomic group of insects, but are especially commonly found in
the beetles (Coleoptera), two-winged insects (Diptera) and moths
(Lepidoptera).
Transgenic plants containing one or more genes that code for an
insecticidal resistance and express one or more toxins are known
and some of them are commercially available. Examples of such
plants are: YieldGard.RTM. (maize variety that expresses a Cry1Ab
toxin); YieldGard Rootworm.RTM. (maize variety that expresses a
Cry3Bb1 toxin); YieldGard Plus.RTM. (maize variety that expresses a
Cry1Ab and a Cry3Bb1 toxin); Starlink.RTM. (maize variety that
expresses a Cry9C toxin); Herculex I.RTM. (maize variety that
expresses a Cry1Fa2 toxin and the enzyme phosphinothricine
N-acetyltransferase (PAT) to achieve tolerance to the herbicide
glufosinate ammonium); NuCOTN 33B.RTM. (cotton variety that
expresses a Cry1Ac toxin); Bollgard I.RTM. (cotton variety that
expresses a Cry1Ac toxin); Bollgard II.RTM. (cotton variety that
expresses a Cry1Ac and a Cry2Ab toxin); VipCot.RTM. (cotton variety
that expresses a Vip3A and a Cry1Ab toxin); NewLeaf.RTM. (potato
variety that expresses a Cry3A toxin); NatureGard.RTM.,
Agrisure.RTM. GT Advantage (GA21 glyphosate-tolerant trait),
Agrisure.RTM. CB Advantage (Btl 1 corn borer (CB) trait) and
Protecta.RTM..
Further examples of such transgenic crops are:
1. Bt11 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31
790 St. Sauveur, France, registration number C/FR/96/05/10.
Genetically modified Zea mays which has been rendered resistant to
attack by the European corn borer (Ostrinia nubilalis and Sesamia
nonagrioides) by transgenic expression of a truncated Cry1Ab toxin.
Btl 1 maize also transgenically expresses the enzyme PAT to achieve
tolerance to the herbicide glufosinate ammonium.
2. Bt176 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31
790 St. Sauveur, France, registration number C/FR/96/05/10.
Genetically modified Zea mays which has been rendered resistant to
attack by the European corn borer (Ostrinia nubilalis and Sesamia
nonagrioides) by transgenic expression of a Cry1Ab toxin. Bt176
maize also transgenically expresses the enzyme PAT to achieve
tolerance to the herbicide glufosinate ammonium.
3. MIR604 Maize from Syngenta Seeds SAS, Chemin de I'Hobit 27, F-31
790 St. Sauveur, France, registration number C/FR/96/05/10. Maize
which has been rendered insect-resistant by transgenic expression
of a modified Cry3A toxin. This toxin is Cry3A055 modified by
insertion of a cathepsin-G-protease recognition sequence. The
preparation of such transgenic maize plants is described in WO
03/018810.
4. MON 863 Maize from Monsanto Europe S.A. 270-272 Avenue de
Tervuren, B-1150 Brussels, Belgium, registration number C/DE/02/9.
MON 863 expresses a Cry3Bb1 toxin and has resistance to certain
Coleoptera insects.
5. IPC 531 Cotton from Monsanto Europe S.A. 270-272 Avenue de
Tervuren, B-1150 Brussels, Belgium, registration number
C/ES/96/02.
6. 1507 Maize from Pioneer Overseas Corporation, Avenue Tedesco, 7
B-1160 Brussels, Belgium, registration number C/NL/00/10.
Genetically modified maize for the expression of the protein Cry1F
for achieving resistance to certain Lepidoptera insects and of the
PAT protein for achieving tolerance to the herbicide glufosinate
ammonium.
7. NK603.times.MON 810 Maize from Monsanto Europe S.A. 270-272
Avenue de Tervuren, B-1150 Brussels, Belgium, registration number
C/GB/02/M3/03. Consists of conventionally bred hybrid maize
varieties by crossing the genetically modified varieties NK603 and
MON 810. NK603.times.MON 810 Maize transgenically expresses the
protein CP4 EPSPS, obtained from Agrobacterium sp. strain CP4,
which imparts tolerance to the herbicide Roundup.RTM. (contains
glyphosate), and also a Cry1Ab toxin obtained from Bacillus
thuringiensis subsp. kurstaki which brings about tolerance to
certain Lepidoptera, include the European corn borer.
Transgenic crops of insect-resistant plants are also described in
BATS (Zentrum fur Biosicherheit und Nachhaltigkeit, Zentrum BATS,
Clarastrasse 13, 4058 Basel, Switzerland) Report 2003,
(http://bats.ch). The term "crops" is to be understood as including
also crop plants which have been so transformed by the use of
recombinant DNA techniques that they are capable of synthesising
antipathogenic substances having a selective action, such as, for
example, the so-called "pathogenesis-related proteins" (PRPs, see
e.g. EP-A-0 392 225). Examples of such antipathogenic substances
and transgenic plants capable of synthesising such antipathogenic
substances are known, for example, from EP-A-0 392 225, WO 95/33818
and EP-A-0 353 191. The methods of producing such transgenic plants
are generally known to the person skilled in the art and are
described, for example, in the publications mentioned above.
Crops may also be modified for enhanced resistance to fungal (for
example Fusarium, Anthracnose, or Phytophthora), bacterial (for
example Pseudomonas) or viral (for example potato leafroll virus,
tomato spotted wilt virus, cucumber mosaic virus) pathogens.
Crops also include those that have enhanced resistance to
nematodes, such as the soybean cyst nematode.
Crops that are tolerance to abiotic stress include those that have
enhanced tolerance to drought, high salt, high temperature, chill,
frost, or light radiation, for example through expression of NF--YB
or other proteins known in the art.
Antipathogenic substances which can be expressed by such transgenic
plants include, for example, ion channel blockers, such as blockers
for sodium and calcium channels, for example the viral KP1, KP4 or
KP6 toxins; stilbene synthases; bibenzyl synthases; chitinases;
glucanases; the so-called "pathogenesis-related proteins" (PRPs;
see e.g. EP-A-0 392 225); antipathogenic substances produced by
microorganisms, for example peptide antibiotics or heterocyclic
antibiotics (see e.g. WO 95/33818) or protein or polypeptide
factors involved in plant pathogen defence (so-called "plant
disease resistance genes", as described in WO 03/000906).
Further areas of use of the compositions according to the invention
are the protection of stored goods and store ambients and the
protection of raw materials, such as wood, textiles, floor
coverings or buildings, and also in the hygiene sector, especially
the protection of humans, domestic animals and productive livestock
against pests of the mentioned type.
The present invention also provides a method for controlling pests
(such as mosquitoes and other disease vectors; see also
http://www.who.int/malaria/vector_control/irs/en/). In one
embodiment, the method for controlling pests comprises applying the
compositions of the invention to the target pests, to their locus
or to a surface or substrate by brushing, rolling, spraying,
spreading or dipping. By way of example, an IRS (indoor residual
spraying) application of a surface such as a wall, ceiling or floor
surface is contemplated by the method of the invention. In another
embodiment, it is contemplated to apply such compositions to a
substrate such as non-woven or a fabric material in the form of (or
which can be used in the manufacture of) netting, clothing,
bedding, curtains and tents. A further object of the invention is
therefore a substrate selected from nonwoven and fabric material
comprising a composition which contains a compound of formula
I.
In one embodiment, the method for controlling such pests comprises
applying a pesticidally effective amount of the compositions of the
invention to the target pests, to their locus, or to a surface or
substrate so as to provide effective residual pesticidal activity
on the surface or substrate. Such application may be made by
brushing, rolling, spraying, spreading or dipping the pesticidal
composition of the invention. By way of example, an IRS application
of a surface such as a wall, ceiling or floor surface is
contemplated by the method of the invention so as to provide
effective residual pesticidal activity on the surface. In another
embodiment, it is contemplated to apply such compositions for
residual control of pests on a substrate such as a fabric material
in the form of (or which can be used in the manufacture of)
netting, clothing, bedding, curtains and tents.
Substrates including non-woven, fabrics or netting to be treated
may be made of natural fibres such as cotton, raffia, jute, flax,
sisal, hessian, or wool, or synthetic fibres such as polyamide,
polyester, polypropylene, polyacrylonitrile or the like. The
polyesters are particularly suitable. The methods of textile
treatment are known, e.g. WO 2008/151984, WO 2003/034823, U.S. Pat.
No. 5,631,072, WO 2005/64072, WO 2006/128870, EP 1724392,
WO2005113886 or WO 2007/090739.
Further areas of use of the compositions according to the invention
are the field of tree injection/trunk treatment for all ornamental
trees as well all sort of fruit and nut trees.
In the field of tree injection/trunk treatment, the compounds
according to the present invention are especially suitable against
wood-boring insects from the order Lepidoptera as mentioned above
and from the order Coleoptera, especially against woodborers listed
in the following tables A and B:
TABLE-US-00005 TABLE A Examples of exotic woodborers of economic
importance. Family Species Host or Crop Infested Buprestidae
Agrilus planipennis Ash Cerambycidae Anoplura glabripennis
Hardwoods Scolytidae Xylosandrus crassiusculus Hardwoods X.
mutilatus Hardwoods Tomicus piniperda Conifers
TABLE-US-00006 TABLE B Examples of native woodborers of economic
importance. Family Species Host or Crop Infested Buprestidae
Agrilus anxius Birch Agrilus politus Willow, Maple Agrilus sayi
Bayberry, Sweetfern Agrilus vittaticolllis Apple, Pear, Cranberry,
Serviceberry, Hawthorn Chrysobothris femorata Apple, Apricot,
Beech, Boxelder, Cherry, Chestnut, Currant, Elm, Hawthorn,
Hackberry, Hickory, Horsechestnut, Linden, Maple, Mountain-ash,
Oak, Pecan, Pear, Peach, Persimmon, Plum, Poplar, Quince, Redbud,
Serviceberry, Sycamore, Walnut, Willow Texania campestris Basswood,
Beech, Maple, Oak, Sycamore, Willow, Yellow-poplar Cerambycidae
Goes pulverulentus Beech, Elm, Nuttall, Willow, Black oak,
Cherrybark oak, Water oak, Sycamore Goes tigrinus Oak Neoclytus
acuminatus Ash, Hickory, Oak, Walnut, Birch, Beech, Maple, Eastern
hophornbeam, Dogwood, Persimmon, Redbud, Holly, Hackberry, Black
locust, Honeylocust, Yellow-poplar, Chestnut, Osage-orange,
Sassafras, Lilac, Mountain-mahogany, Pear, Cherry, Plum, Peach,
Apple, Elm, Basswood, Sweetgum Neoptychodes trilineatus Fig, Alder,
Mulberry, Willow, Netleaf hackberry Oberea ocellata Sumac, Apple,
Peach, Plum, Pear, Currant, Blackberry Oberea tripunctata Dogwood,
Viburnum, Elm, Sourwood, Blueberry, Rhododendron, Azalea, Laurel,
Poplar, Willow, Mulberry Oncideres cingulata Hickory, Pecan,
Persimmon, Elm, Sourwood, Basswood, Honeylocust, Dogwood,
Eucalyptus, Oak, Hackberry, Maple, Fruit trees Saperda calcarata
Poplar Strophiona nitens Chestnut, Oak, Hickory, Walnut, Beech,
Maple Scolytidae Corthylus columbianus Maple, Oak, Yellow-poplar,
Beech, Boxelder, Sycamore, Birch, Basswood, Chestnut, Elm
Dendroctonus frontalis Pine Dlyocoetes betulae Birch, Sweetgum,
Wild cherry, Beech, Pear Monarthrum fasciatum Oak, Maple, Birch,
Chestnut, Sweetgum, Blackgum, Poplar, Hickory, Mimosa, Apple,
Peach, Pine Phloeotribus liminaris Peach, Cherry, Plum, Black
cherry, Elm, Mulberry, Mountain-ash Pseudopityophthorus pruinosus
Oak, American beech, Black cherry, Chickasaw plum, Chestnut, Maple,
Hickory, Hornbeam, Hophornbeam Sesiidae Paranthrene simulans Oak,
American chestnut Sannina uroceriformis Persimmon Synanthedon
exitiosa Peach, Plum, Nectarine, Cherry, Apricot, Almond, Black
cherry Synanthedon pictipes Peach, Plum, Cherry, Beach, Black
Cherry Synanthedon rubrofascia Tupelo Synanthedon scitula Dogwood,
Pecan, Hickory, Oak, Chestnut, Beech, Birch, Black cherry, Elm,
Mountain-ash, Viburnum, Willow, Apple, Loquat, Ninebark, Bayberry
Vitacea polistiformis Grape
The present invention may be also used to control any insect pests
that may be present in turfgrass, including for example beetles,
caterpillars, fire ants, ground pearls, millipedes, sow bugs,
mites, mole crickets, scales, mealybugs ticks, spittlebugs,
southern chinch bugs and white grubs. The present invention may be
used to control insect pests at various stages of their life cycle,
including eggs, larvae, nymphs and adults.
In particular, the present invention may be used to control insect
pests that feed on the roots of turfgrass including white grubs
(such as Cyclocephala spp. (e.g. masked chafer, C. lurida),
Rhizotrogus spp. (e.g. European chafer, R. majalis), Cotinus spp.
(e.g. Green June beetle, C. nitida), Popillia spp. (e.g. Japanese
beetle, P. japonica), Phyllophaga spp. (e.g. May/June beetle),
Ataenius spp. (e.g. Black turfgrass ataenius, A. spretulus),
Maladera spp. (e.g. Asiatic garden beetle, M. castanea) and Tomarus
spp.), ground pearls (Margarodes spp.), mole crickets (tawny,
southern, and short-winged; Scapteriscus spp., Gryllotalpa
africana) and leatherjackets (European crane fly, Tipula spp.).
The present invention may also be used to control insect pests of
turfgrass that are thatch dwelling, including armyworms (such as
fall armyworm Spodoptera frugiperda, and common armyworm
Pseudaletia unipuncta), cutworms, billbugs (Sphenophorus spp., such
as S. venatus verstitus and S. parvulus), and sod webworms (such as
Crambus spp. and the tropical sod webworm, Herpetogramma
phaeopteralis).
The present invention may also be used to control insect pests of
turfgrass that live above the ground and feed on the turfgrass
leaves, including chinch bugs (such as southern chinch bugs,
Blissus insularis), Bermudagrass mite (Eriophyes cynodoniensis),
rhodesgrass mealybug (Antonina graminis), two-lined spittlebug
(Propsapia bicincta), leafhoppers, cutworms (Noctuidae family), and
greenbugs.
The present invention may also be used to control other pests of
turfgrass such as red imported fire ants (Solenopsis invicta) that
create ant mounds in turf.
In the hygiene sector, the compositions according to the invention
are active against ectoparasites such as hard ticks, soft ticks,
mange mites, harvest mites, flies (biting and licking), parasitic
fly larvae, lice, hair lice, bird lice and fleas.
Examples of such parasites are:
Of the order Anoplurida: Haematopinus spp., Linognathus spp.,
Pediculus spp. and Phtirus spp., Solenopotes spp.
In the hygiene sector, the compositions according to the invention
are active against ectoparasites such as hard ticks, soft ticks,
mange mites, harvest mites, flies (biting and licking), parasitic
fly larvae, lice, hair lice, bird lice and fleas.
Examples of such parasites are:
Of the order Anoplurida: Haematopinus spp., Linognathus spp.,
Pediculus spp. and Phtirus spp., Solenopotes spp.
Of the order Mallophagida: Trimenopon spp., Menopon spp., Trinoton
spp., Bovicola spp., Werneckiella spp., Lepikentron spp., Damalina
spp., Trichodectes spp. and Felicola spp.
Of the order Diptera and the suborders Nematocerina and
Brachycerina, for example Aedes spp., Anopheles spp., Culex spp.,
Simulium spp., Eusimulium spp., Phlebotomus spp., Lutzomyia spp.,
Culicoides spp., Chrysops spp., Hybomitra spp., Atylotus spp.,
Tabanus spp., Haematopota spp., Philipomyia spp., Braula spp.,
Musca spp., Hydrotaea spp., Stomoxys spp., Haematobia spp.,
Morellia spp., Fannia spp., Glossina spp., Calliphora spp., Lucilia
spp., Chrysomyia spp., Wohlfahrtia spp., Sarcophaga spp., Oestrus
spp., Hypoderma spp., Gasterophilus spp., Hippobosca spp.,
Lipoptena spp. and Melophagus spp.
Of the order Siphonapterida, for example Pulex spp.,
Ctenocephalides spp., Xenopsylla spp., Ceratophyllus spp.
Of the order Heteropterida, for example Cimex spp., Triatoma spp.,
Rhodnius spp., Panstrongylus spp.
Of the order Blattarida, for example Blatta orientalis, Periplaneta
americana, Blattelagermanica and Supella spp.
Of the subclass Acaria (Acarida) and the orders Meta- and
Meso-stigmata, for example Argas spp., Ornithodorus spp., Otobius
spp., Ixodes spp., Amblyomma spp., Boophilus spp., Dermacentor
spp., Haemophysalis spp., Hyalomma spp., Rhipicephalus spp.,
Dermanyssus spp., Raillietia spp., Pneumonyssus spp., Stemostoma
spp. and Varroa spp.
Of the orders Actinedida (Prostigmata) and Acaridida (Astigmata),
for example Acarapis spp., Cheyletiella spp., Ornithocheyletia
spp., Myobia spp., Psorergatesspp., Demodexspp., Trombicula spp.,
Listrophorus spp., Acarus spp., Tyrophagus spp., Caloglyphus spp.,
Hypodectes spp., Pterolichus spp., Psoroptes spp., Chorioptes spp.,
Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp.,
Cytodites spp. and Laminosioptes spp.
The compositions according to the invention are also suitable for
protecting against insect infestation in the case of materials such
as wood, textiles, plastics, adhesives, glues, paints, paper and
card, leather, floor coverings and buildings.
The compositions according to the invention can be used, for
example, against the following pests: beetles such as Hylotrupes
bajulus, Chlorophorus pilosis, Anobium punctatum, Xestobium
rufovillosum, Ptilinuspecticornis, Dendrobium pertinex, Ernobius
mollis, Priobium carpini, Lyctus brunneus, Lyctus africanus, Lyctus
planicollis, Lyctus linearis, Lyctus pubescens, Trogoxylon aequale,
Minthesrugicollis, Xyleborus spec., Tryptodendron spec., Apate
monachus, Bostrychus capucins, Heterobostrychus brunneus, Sinoxylon
spec. and Dinoderus minutus, and also hymenopterans such as Sirex
juvencus, Urocerus gigas, Urocerus gigas taignus and Urocerus
augur, and termites such as Kalotermes flavicollis, Cryptotermes
brevis, Heterotermes indicola, Reticulitermes flavipes,
Reticulitermes santonensis, Reticulitermes lucifugus, Mastotermes
darwiniensis, Zootermopsis nevadensis and Coptotermes formosanus,
and bristletails such as Lepisma saccharina.
The compounds according to the invention can be used as pesticidal
agents in unmodified form, but they are generally formulated into
compositions in various ways using formulation adjuvants, such as
carriers, solvents and surface-active substances. The formulations
can be in various physical forms, e.g. in the form of dusting
powders, gels, wettable powders, water-dispersible granules,
water-dispersible tablets, effervescent pellets, emulsifiable
concentrates, microemulsifiable concentrates, oil-in-water
emulsions, oil-flowables, aqueous dispersions, oily dispersions,
suspo-emulsions, capsule suspensions, emulsifiable granules,
soluble liquids, water-soluble concentrates (with water or a
water-miscible organic solvent as carrier), impregnated polymer
films or in other forms known e.g. from the Manual on Development
and Use of FAO and WHO Specifications for Pesticides, United
Nations, First Edition, Second Revision (2010). Such formulations
can either be used directly or diluted prior to use. The dilutions
can be made, for example, with water, liquid fertilisers,
micronutrients, biological organisms, oil or solvents.
The formulations can be prepared e.g. by mixing the active
ingredient with the formulation adjuvants in order to obtain
compositions in the form of finely divided solids, granules,
solutions, dispersions or emulsions. The active ingredients can
also be formulated with other adjuvants, such as finely divided
solids, mineral oils, oils of vegetable or animal origin, modified
oils of vegetable or animal origin, organic solvents, water,
surface-active substances or combinations thereof.
The active ingredients can also be contained in very fine
microcapsules. Microcapsules contain the active ingredients in a
porous carrier. This enables the active ingredients to be released
into the environment in controlled amounts (e.g. slow-release).
Microcapsules usually have a diameter of from 0.1 to 500 microns.
They contain active ingredients in an amount of about from 25 to
95% by weight of the capsule weight. The active ingredients can be
in the form of a monolithic solid, in the form of fine particles in
solid or liquid dispersion or in the form of a suitable solution.
The encapsulating membranes can comprise, for example, natural or
synthetic rubbers, cellulose, styrene/butadiene copolymers,
polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas,
polyurethane or chemically modified polymers and starch xanthates
or other polymers that are known to the person skilled in the art.
Alternatively, very fine microcapsules can be formed in which the
active ingredient is contained in the form of finely divided
particles in a solid matrix of base substance, but the
microcapsules are not themselves encapsulated. The formulation
adjuvants that are suitable for the preparation of the compositions
according to the invention are known per se. As liquid carriers
there may be used: water, toluene, xylene, petroleum ether,
vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid
anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone,
butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl
esters of acetic acid, diacetone alcohol, 1,2-dichloropropane,
diethanolamine, p-diethylbenzene, diethylene glycol, diethylene
glycol abietate, diethylene glycol butyl ether, diethylene glycol
ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide,
dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene
glycol methyl ether, dipropylene glycol dibenzoate, diproxitol,
alkylpyrrolidone, ethyl acetate, 2-ethyl-hexanol, ethylene
carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha-pinene,
d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl
ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol,
glycerol acetate, glycerol diacetate, glycerol triacetate,
hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate,
isooctane, isophorone, isopropylbenzene, isopropyl myristate,
lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl
isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl
octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane,
n-octylamine, octadecanoic acid, octylamine acetate, oleic acid,
oleylamine, o-xylene, phenol, polyethylene glycol, propionic acid,
propyl lactate, propylene carbonate, propylene glycol, propylene
glycol methyl ether, p-xylene, toluene, triethyl phosphate,
triethylene glycol, xylenesulfonic acid, paraffin, mineral oil,
trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate,
butyl acetate, propylene glycol methyl ether, diethylene glycol
methyl ether, methanol, ethanol, isopropanol, and alcohols of
higher molecular weight, such as amyl alcohol, tetrahydrofurfuryl
alcohol, hexanol, octanol, ethylene glycol, propylene glycol,
glycerol, N-methyl-2-pyrrolidone and the like.
Suitable solid carriers are, for example, talc, titanium dioxide,
pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone,
calcium carbonate, bentonite, calcium montmorillonite, cottonseed
husks, wheat flour, soybean flour, pumice, wood flour, ground
walnut shells, lignin and similar substances.
A large number of surface-active substances can advantageously be
used in both solid and liquid formulations, especially in those
formulations which can be diluted with a carrier prior to use.
Surface-active substances may be anionic, cationic, non-ionic or
polymeric and they can be used as emulsifiers, wetting agents or
suspending agents or for other purposes. Typical surface-active
substances include, for example, salts of alkyl sulfates, such as
diethanolammonium lauryl sulfate; salts of alkylarylsulfonates,
such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide
addition products, such as nonylphenol ethoxylate; alcohol/alkylene
oxide addition products, such as tridecylalcohol ethoxylate; soaps,
such as sodium stearate; salts of alkylnaphthalenesulfonates, such
as sodium dibutylnaphthalenesulfonate; dialkyl esters of
sulfosuccinate salts, such as sodium
di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol
oleate; quaternary amines, such as lauryltrimethylammonium
chloride, polyethylene glycol esters of fatty acids, such as
polyethylene glycol stearate; block copolymers of ethylene oxide
and propylene oxide; and salts of mono- and di-alkylphosphate
esters; and also further substances described e.g. in McCutcheon's
Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood
N.J. (1981).
Further adjuvants that can be used in pesticidal formulations
include crystallisation inhibitors, viscosity modifiers, suspending
agents, dyes, anti-oxidants, foaming agents, light absorbers,
mixing auxiliaries, antifoams, complexing agents, neutralising or
pH-modifying substances and buffers, corrosion inhibitors,
fragrances, wetting agents, take-up enhancers, micronutrients,
plasticisers, glidants, lubricants, dispersants, thickeners,
antifreezes, microbicides, and liquid and solid fertilisers.
The compositions according to the invention can include an additive
comprising an oil of vegetable or animal origin, a mineral oil,
alkyl esters of such oils or mixtures of such oils and oil
derivatives. The amount of oil additive in the composition
according to the invention is generally from 0.01 to 10%, based on
the mixture to be applied. For example, the oil additive can be
added to a spray tank in the desired concentration after a spray
mixture has been prepared. Preferred oil additives comprise mineral
oils or an oil of vegetable origin, for example rapeseed oil, olive
oil or sunflower oil, emulsified vegetable oil, alkyl esters of
oils of vegetable origin, for example the methyl derivatives, or an
oil of animal origin, such as fish oil or beef tallow. Preferred
oil additives comprise alkyl esters of C.sub.8-C.sub.22 fatty
acids, especially the methyl derivatives of C.sub.12-C.sub.18 fatty
acids, for example the methyl esters of lauric acid, palmitic acid
and oleic acid (methyl laurate, methyl palmitate and methyl oleate,
respectively). Many oil derivatives are known from the Compendium
of Herbicide Adjuvants, 10.sup.th Edition, Southern Illinois
University, 2010. The inventive compositions generally comprise
from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, of
compounds of the present invention and from 1 to 99.9% by weight of
a formulation adjuvant which preferably includes from 0 to 25% by
weight of a surface-active substance. Whereas commercial products
may preferably be formulated as concentrates, the end user will
normally employ dilute formulations.
The rates of application vary within wide limits and depend on the
nature of the soil, the method of application, the crop plant, the
pest to be controlled, the prevailing climatic conditions, and
other factors governed by the method of application, the time of
application and the target crop. As a general guideline compounds
may be applied at a rate of from 1 to 2000 l/ha, especially from 10
to 1000 l/ha.
Preferred formulations can have the following compositions (weight
%):
Emulsifiable Concentrates:
active ingredient: 1 to 95%, preferably 60 to 90%
surface-active agent: 1 to 30%, preferably 5 to 20%
liquid carrier: 1 to 80%, preferably 1 to 35%
Dusts:
active ingredient: 0.1 to 10%, preferably 0.1 to 5%
solid carrier: 99.9 to 90%, preferably 99.9 to 99%
Suspension Concentrates:
active ingredient: 5 to 75%, preferably 10 to 50%
water: 94 to 24%, preferably 88 to 30%
surface-active agent: 1 to 40%, preferably 2 to 30%
Wettable Powders:
active ingredient: 0.5 to 90%, preferably 1 to 80%
surface-active agent: 0.5 to 20%, preferably 1 to 15%
solid carrier: 5 to 95%, preferably 15 to 90%
Granules:
active ingredient: 0.1 to 30%, preferably 0.1 to 15%
solid carrier: 99.5 to 70%, preferably 97 to 85%
The following Examples further illustrate, but do not limit, the
invention.
TABLE-US-00007 Wettable powders a) b) c) active ingredients 25% 50%
75% sodium lignosulfonate 5% 5% -- sodium lauryl sulfate 3% -- 5%
sodium diisobutylnaphthalenesulfonate -- 6% 10% phenol polyethylene
glycol ether (7-8 mol of -- 2% -- ethylene oxide) highly dispersed
silicic acid 5% 10% 10% Kaolin 62% 27% --
The combination is thoroughly mixed with the adjuvants and the
mixture is thoroughly ground in a suitable mill, affording wettable
powders that can be diluted with water to give suspensions of the
desired concentration.
TABLE-US-00008 Powders for dry seed treatment a) b) c) active
ingredients 25% 50% 75% light mineral oil 5% 5% 5% highly dispersed
silicic acid 5% 5% -- Kaolin 65% 40% -- Talcum -- 20
The combination is thoroughly mixed with the adjuvants and the
mixture is thoroughly ground in a suitable mill, affording powders
that can be used directly for seed treatment.
TABLE-US-00009 Emulsifiable concentrate active ingredients 10%
octylphenol polyethylene glycol ether (4-5 mol of ethylene 3%
oxide) calcium dodecylbenzenesulfonate 3% castor oil polyglycol
ether (35 mol of ethylene oxide) 4% Cyclohexanone 30% xylene
mixture 50%
Emulsions of any required dilution, which can be used in plant
protection, can be obtained from this concentrate by dilution with
water.
TABLE-US-00010 Dusts a) b) c) Active ingredients 5% 6% 4% Talcum
95% -- -- Kaolin -- 94% -- mineral filler -- -- 96%
Ready-for-use dusts are obtained by mixing the combination with the
carrier and grinding the mixture in a suitable mill. Such powders
can also be used for dry dressings for seed.
TABLE-US-00011 Extruder granules Active ingredients 15% sodium
lignosulfonate 2% carboxymethylcellulose 1% Kaolin 82%
The combination is mixed and ground with the adjuvants, and the
mixture is moistened with water. The mixture is extruded and then
dried in a stream of air.
TABLE-US-00012 Coated granules Active ingredients 8% polyethylene
glycol (mol. wt. 200) 3% Kaolin 89%
The finely ground combination is uniformly applied, in a mixer, to
the kaolin moistened with polyethylene glycol. Non-dusty coated
granules are obtained in this manner.
TABLE-US-00013 Suspension concentrate active ingredients 40%
propylene glycol 10% nonylphenol polyethylene glycol ether (15 mol
of ethylene oxide) 6% Sodium lignosulfonate 10%
carboxymethylcellulose 1% silicone oil (in the form of a 75%
emulsion in water) 1% Water 32%
The finely ground combination is intimately mixed with the
adjuvants, giving a suspension concentrate from which suspensions
of any desired dilution can be obtained by dilution with water.
Using such dilutions, living plants as well as plant propagation
material can be treated and protected against infestation by
microorganisms, by spraying, pouring or immersion.
TABLE-US-00014 Flowable concentrate for seed treatment active
ingredients 40% propylene glycol 5% copolymer butanol PO/EO 2%
Tristyrenephenole with 10-20 moles EO 2% 1,2-benzisothiazolin-3-one
(in the form of a 20% solution in 0.5% water) monoazo-pigment
calcium salt 5% Silicone oil (in the form of a 75% emulsion in
water) 0.2% Water 45.3%
The finely ground combination is intimately mixed with the
adjuvants, giving a suspension concentrate from which suspensions
of any desired dilution can be obtained by dilution with water.
Using such dilutions, living plants as well as plant propagation
material can be treated and protected against infestation by
microorganisms, by spraying, pouring or immersion.
Slow Release Capsule Suspension
28 parts of the combination are mixed with 2 parts of an aromatic
solvent and 7 parts of toluene
diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This
mixture is emulsified in a mixture of 1.2 parts of
polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water
until the desired particle size is achieved. To this emulsion a
mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is
added. The mixture is agitated until the polymerization reaction is
completed. The obtained capsule suspension is stabilized by adding
0.25 parts of a thickener and 3 parts of a dispersing agent. The
capsule suspension formulation contains 28% of the active
ingredients. The medium capsule diameter is 8-15 microns. The
resulting formulation is applied to seeds as an aqueous suspension
in an apparatus suitable for that purpose.
Formulation types include an emulsion concentrate (EC), a
suspension concentrate (SC), a suspo-emulsion (SE), a capsule
suspension (CS), a water dispersible granule (WG), an emulsifiable
granule (EG), an emulsion, water in oil (EO), an emulsion, oil in
water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil
miscible flowable (OF), an oil miscible liquid (OL), a soluble
concentrate (SL), an ultra-low volume suspension (SU), an ultra-low
volume liquid (UL), a technical concentrate (TK), a dispersible
concentrate (DC), a wettable powder (WP), a soluble granule (SG) or
any technically feasible formulation in combination with
agriculturally acceptable adjuvants.
PREPARATORY EXAMPLES
"Mp" means melting point in .degree. C. Free radicals represent
methyl groups. .sup.1H and .sup.19F NMR measurements were recorded
on Brucker 400 MHz or 300 MHz spectrometers, chemical shifts are
given in ppm relevant to a TMS standard. Spectra measured in
deuterated solvents as indicated.
LCMS Methods:
Method A--Standard:
Spectra were recorded on a Mass Spectrometer from Waters (SQD or ZQ
Single quadrupole mass spectrometer) equipped with an electrospray
source (Polarity: positive or negative ions, Capillary: 3.00 kV,
Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature:
150.degree. C., Desolvation Temperature: 350.degree. C., Cone Gas
Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to
900 Da) and an Acquity UPLC from Waters: Binary pump, heated column
compartment and diode-array detector. Solvent degasser, binary
pump, heated column compartment and diode-array detector. Column:
Waters UPLC HSS T3, 1.8 .quadrature.m, 30.times.2.1 mm, Temp:
60.degree. C., DAD Wavelength range (nm): 210 to 500, Solvent
Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05%
HCOOH:gradient:gradient: 0 min 0% B, 100% A; 1.2-1.5 min 100% B;
Flow (ml/min) 0.85.
Method B--Standard Long:
Spectra were recorded on a Mass Spectrometer from Waters (SQD or ZQ
Single quadrupole mass spectrometer) equipped with an electrospray
source (Polarity: positive or negative ions, Capillary: 3.00 kV,
Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature:
150.degree. C., Desolvation Temperature: 350.degree. C., Cone Gas
Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to
900 Da) and an Acquity UPLC from Waters: Binary pump, heated column
compartment and diode-array detector. Solvent degasser, binary
pump, heated column compartment and diode-array detector. Column:
Waters UPLC HSS T3, 1.8 .quadrature.m, 30.times.2.1 mm, Temp:
60.degree. C., DAD Wavelength range (nm): 210 to 500, Solvent
Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05%
HCOOH:gradient:gradient: 0 min 0% B, 100% A; 2.7-3.0 min 100% B;
Flow (ml/min) 0.85
Method C--Unpolar:
Spectra were recorded on a Mass Spectrometer from Waters (SQD or ZQ
Single quadrupole mass spectrometer) equipped with an electrospray
source (Polarity: positive or negative ions, Capillary: 3.00 kV,
Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature:
150.degree. C., Desolvation Temperature: 350.degree. C., Cone Gas
Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to
900 Da) and an Acquity UPLC from Waters: Binary pump, heated column
compartment and diode-array detector. Solvent degasser, binary
pump, heated column compartment and diode-array detector. Column:
Waters UPLC HSS T3, 1.8 .quadrature.m, 30.times.2.1 mm, Temp:
60.degree. C., DAD Wavelength range (nm): 210 to 500, Solvent
Gradient: A=water+5% MeOH+0.05% HCOOH, B=Acetonitrile+0.05%
HCOOH:gradient:gradient: 0 min 40% B, 60% A; 1.2-1.5 min 100% B;
Flow (ml/min) 0.85
Synthesis of Intermediates:
Intermediate 1: Synthesis of 3-ethylsulfanylquinoline-2-carboxylic
acid
Step A: ethyl 3-ethylsulfanylquinoline-2-carboxylate
##STR00086##
To stirred solution of compound 1 (3.6 g, 16.66 mmol) in DCE (30
ml) was added diethyldisulfide (4.51 ml, 36.6 mmol), t-butyl
nitrite was then added dropwise at ambient temperature. The
reaction mixture was heated to 40.degree. C. for 2 hours. Reaction
was monitored by TLC. After completion of the starting material,
reaction mixture was diluted with CH.sub.2Cl.sub.2 and washed with
water (2.times.10 mL). Organic layer was dried over
Na.sub.2SO.sub.4. Filtered, concentrated and purified by column
chromatography using hexane-ethyl acetate (100-200 silica gel) to
give the desired compound as a yellow liquid (amount: 1.0 g;
Yield=23%). .sup.1H NMR (400 MHz, CDCl.sub.3): .delta. (ppm) 8.14
(d, 1H), 8.06 (s, 1H), 7.75 (d, 1H), 7.68 (m, 1H), 7.58 (m, 1H),
4.54 (q, 2H), 3.03 (q, 2H), 1.48 (t, 3H), 1.40 (t, 3H).
Step B: 3-ethylsulfanylquinoline-2-carboxylic acid
##STR00087## To as stirred solution of compound 3 (1 g, 3.8 mmol)
in THF (8 ml) was added NaOH (2 N, 2.2 eq) at RT.
Reaction mixture was stirred for 16 hours at ambient temperature.
Reaction was monitored by TLC. After completion of the starting
material, reaction mixture was extracted with ethyl acetate
(2.times.10 mL). Water part was then acidified to pH=4 by 10%
citric acid solution and extracted with ethyl acetate (3.times.20
ml). Organic layer was dried over Na.sub.2SO.sub.4. Filtered,
concentrated under reduced pressure to give the crude solid, which
was triturated with ether to give the desired compound as yellow
solid (amount: 613 mg; Yield=68%). .sup.1H NMR (400 MHz,
DMSO-d.sub.6): .delta. (ppm) 13.7 (s, 1H), 8.42 (s, 1H), 8.00 (m,
2H), 7.75 (m, 1H), 7.68 (m, 1H), 3.09 (q, 2H), 1.29 (t, 3H).
Intermediate 2: Synthesis of 3-ethylsulfanylnaphtalene-2-carboxylic
acid
Step A: 3-sulfanylnaphthalene-2-carboxylic acid
##STR00088##
To a stirred suspension of compound-1 (10 g, 53.47 mmol) in water
(28 mL) and concentrate HCl (11.4 mL) at 5.degree. C. was added
dropwise a solution of NaNO.sub.2 (3.69 g, 53.47 mmol) in water
(14.6 mL) and the solution maintained at 5.degree. C. Crushed ice
was added to the reaction mixture periodically during addition to
keep the temperature below 5.degree. C. Meanwhile,
Na.sub.2S.9H.sub.2O (13.7 g, 176.47 mmol) and sublimed sulfur (1.88
g, 58.82 mmol) were dissolved in water (15 mL) by heating and made
alkaline by addition of NaOH (10 M, 5.5 mL), and the resulting
alkaline disulfide solution was cooled to 5.degree. C. in an ice
bath. The cold diazo solution was added to the alkaline disulfide
solution dropwise with crushed ice added periodically to maintain
the temperature below 5.degree. C. Following addition of the diazo
solution, the mixture was stirred at ambient temperature until
evolution of N.sub.2 gas stopped. Concentrated HCl was added to the
solution until precipitation of the crude product as a yellow solid
was complete. The precipitate was collected and boiled in a
saturated solution of NaHCO3 (130 mL). After being boiled for 15
min, the mixture was filtered to remove the insoluble material, and
conc. HCl was added to the filtrate until the crude product
precipitated out as a yellow solid. Excess conc. HCl was added to
the mixture until precipitation was completed, and the precipitate
was isolated by filtration. This material was boiled in absolute
EtOH (50 mL) for 15 min and filtered and the filtrate concentrated
under reduced pressure to yield the dithiosalicylic acid derivative
The dithiosalicylic acid derivative was then mixed with Zn dust
(3.2 g) in glacial CH.sub.3COOH (50 mL) and refluxed for 48 hours.
The mixture was then cooled and filtered. The solid collected in
this manner was boiled in 5 M NaOH (100 mL). After being boiled for
30 min, the undissolved solid was removed by filtration and the
clear filtrate acidified with concentrated HCl until the crude
product precipitated out as a yellow solid. Concentrated HCl was
added to the mixture until the precipitation was complete. The
precipitate was collected and boiled in EtOH (40 mL) and filtered
and the filtrate concentrated under reduced pressure to yield the
thiosalicylic acid derivative 2. This material was directly carried
on to the next step without extra purification (amount: 4 g;
Yield=36%).
Step B: 3-ethylsulfanylnaphtalene-2-carboxylic acid
##STR00089##
To a stirred solution of compound 2 (1.9 g, 9.36) in ethanol (10
ml) and NaOH (1 M, 10 mL) was added Etl (0.75 ml, 9.36 mmol) at
ambient temperature. The reaction mixture was stirred for 48 hours.
LC-MS showed desired product was formed. Solvent was evaporated and
the crude was acidified to pH=2, extracted with ethyl acetate
(2.times.30 ml). Ethyl acetate layer was dried over
Na.sub.2SO.sub.4. Filtered, concentrated and purified by column
chromatography using hexane-ethyl acetate (100-200 silica gel) to
give the desired compound as a yellow solid. Yield=amount: 274 mg;
25%. .sup.1H NMR (400 MHz, DMSO-d.sub.6): .delta. (ppm) 13.14 (s,
1H), 8.49 (s, 1H), 7.99 (d, 1H), 7.90 (d, 1H), 7.81 (s, 1H), 7.62
(t, 1H), 7.48 (t, 1H), 3.04 (q, 2H), 1.32 (t, 3H).
Intermediate 3: Synthesis of
7-ethylsulfanylisoquinoline-6-carboxylic acid
##STR00090##
Step A: methyl 7-fluoroisoquinoline-6-carboxylate
##STR00091##
In an autoclave, 6-bromo-7-fluoroisoquinoline (commercially
available or synthesized by analogy with WO08077553, 0.452 mg),
Bis(triphenylphoshine) palladuim dichloride (71.0 mg) and
triethylamine (404.8 mg) were added to methanol (40 mL). Then, the
inert atmosphere of autoclave was replaced by CO and the pressure
in the vessel was 20 bar. The autoclave was heated to 80.degree. C.
for 15 h. The solvent was evaporated and the residue was dissolved
in ethyl acetate. The organic solution was washed with brine, dried
and concentrated under vacuum. The residue was purified by column
chromatography using i-hexane/ethyl 2:1 to give the desired
compound (314 mg, 76.5% yield). .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. ppm 9.27 (s, 1H); 8.60 (d, 1H); 8.50 (d, 1H); 7.73 (d, 1H);
7.68 (d, 1H); 4.02 (s, t).
Step B: methyl 7-ethylsulfanylisoquinoline-6-carboxylate
##STR00092##
The mixture of methyl 7-fluoroisoquinoline-6-carboxylate (324.0
mg), sodium ethanethiolate (162.5 mg) and DMF (3 mL) was stirred at
ambient temperature overnight. The solvent was evaporated after
addition of toluene. The residue was dissolved in ethyl acetate and
washed with water, dried and evaporated under vacuum. The crude
product was purified column chromatography using hexane/ethyl 1:2
to give the desired compound (235 mg, 60.1% yield). .sup.1H NMR
(400 MHz, CDCl.sub.3) .delta. ppm 9.21 (s, 1H); 8.52 (d, 1H); 8.42
(s, 1H); 7.76 (s, 1H); 7.64 (d, 1H); 4.00 (s, t); 3.10 (q, 2H);
1.46 (t, 3H).
Step C: 7-ethylsulfanylisoquinoline-6-carboxylic acid
##STR00093##
To a solution of methyl 7-ethylsulfanylisoquinoline-6-carboxylate
(1115.41 mg), in a mixture of water (2 mL) and methanol (20 mL),
was added sodium hydroxide (225.5 mg) at ambient temperature. The
solution was stirred overnight at ambient temperature. The solvent
was evaporated and, after addition of water, the organic phase was
washed with ethyl acetate. The aqueous layer was acidified with
diluted hydrochloric acid (pH 4-5) until precipitation of the
desired product. The yellow precipitate was filtered off and dried
under vacuum and used without extra purification for the next
step.
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. ppm 9.69 (s, 1H); 8.68
(d, 1H); 8.61 (d, 1H); 8.36 (2d, 2H); 3.13 (q, 2H); 1.37 (t,
3H).
Intermediate 4: Synthesis of
5-chloro-3-ethylsulfanyl-quinoline-2-carboxylic acid
##STR00094##
Step A: methyl 3-amino-5-chloro-quinoline-2-carboxylate
##STR00095##
The methyl 3-amino-5-chloro-quinoline-2-carboxylate was synthesised
using a similar protocol as described for the Intermediate 7 (Step
A). .sup.1H NMR (300 MHz, CDCl3) ppm 7.988 (dd, 1H); 7.725 (d, 1H);
7.546 (dd, 1H); 7.341 (dd, 1H); 5.752 (broad s, 2H); 4.556 (q, 2H);
1.534 (t, 3H).
Step B: methyl 5-chloro-3-ethylsulfanyl-quinoline-2-carboxylate
##STR00096##
The ethyl 5-chloro-3-ethylsulfanyl-quinoline-2-carboxylate was
synthesised using a similar protocol as described for the
intermediate 1 (step A): .sup.1H NMR (300 MHz, CDCl3) ppm 8.441 (s,
1H); 8.073 (dd, 1H); 7.663 (d, 1H); 7.590 (dd, 1H); 4.562 (q, 2H);
3.101 (q, 2H); 1.493 (t, 3H); 1.450 (t, 3H).
Step C: 5-chloro-3-ethylsulfanyl-quinoline-2-carboxylic acid
##STR00097##
The 5-chloro-3-ethylsulfanyl-quinoline-2-carboxylic acid was
synthesised using a similar protocol as described for the
Intermediate 7 (Step C): .sup.1H NMR (300 MHz, DMSO) ppm 8.376 (s,
1H); 8.040 (d, 1H); 7.895 (dd, 1H); 7.753 (dd, 1H); 3.157 (q, 2H);
1.333 (t, 3H).
Intermediate 5: Synthesis of
5-bromo-3-ethylsulfanyl-quinoline-2-carboxylic acid
##STR00098##
Step A: ethyl 3-amino-5-bromo-quinoline-2-carboxylate
##STR00099##
The ethyl 3-amino-5-bromo-quinoline-2-carboxylate was synthesised
using a similar protocol as described for the Intermediate 7 (Step
A). .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. ppm 8.03 (dd, 1H);
7.75 (dd, 1H); 7.70 (d, 1H); 7.30 (dd, 1H); 5.76 (sb, 2H); 4.56 (q,
2H); 1.511 (t, 3H).
Step B: ethyl 5-bromo-3-ethylsulfanyl-quinoline-2-carboxylate
##STR00100##
The ethyl 5-bromo-3-ethylsulfanyl-quinoline-2-carboxylate was
synthesised using a similar protocol as described for the
intermediate 1 (step A): .sup.1H NMR (300 MHz, CDCl3) ppm 8.41 (s,
1H); 8.12 (dd, 1H); 7.88 (dd, 1H); 7.53 (dd, 1H); 4.56 (q, 2H),
4.56 (q, 2H); 1.51 (m, 6H).
Step C: 5-bromo-3-ethylsulfanyl-quinoline-2-carboxylic acid
##STR00101##
The 5-bromo-3-ethylsulfanyl-quinoline-2-carboxylic acid was
synthesised using a similar protocol as described for the
Intermediate 7 (Step C): .sup.1H NMR (300 MHz, DMSO) ppm 8.324 (s,
1H); 8.077 (d, 1H); 8.054 (d, 1H); 7.690 (dd, 1H); 3.146 (q, 2H);
1.347 (t, 3H).
Intermediate 6: Synthesis of
6-chloro-3-ethylsulfanyl-quinoline-2-carboxylic acid
##STR00102##
Step A: ethyl 3-amino-6-chloro-quinoline-2-carboxylate
##STR00103##
The ethyl 3-amino-6-chloro-quinoline-2-carboxylate was synthesised
using a similar protocol as described for the Intermediate 7 (Step
A). .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. ppm 7.98 (d, 1H);
7.54 (d, 1H); 7.35 (dd, 1H); 7.24 (s, 1H); 5.67 (sb, 2H), 4.54 (q,
2H); 1.50 (t, 3H).
Step B: ethyl 6-chloro-3-ethylsulfanyl-quinoline-2-carboxylate
##STR00104##
The ethyl 6-chloro-3-ethylsulfanyl-quinoline-2-carboxylate was
synthesised using a similar protocol as described for the
intermediate 1 (step A): .sup.1H NMR (300 MHz, DMSO) ppm 8.45 (s,
1H); 8.14 (d, 1H); 8.05 (d, 1H); 8.77 (dd, 1H); 4.42 (q, 2H); 3.11
(q, 2H); 1.384-1.276 (m, 6H).
Step C: 6-Chloro-3-ethylsulfanyl-quinoline-2-carboxylic acid
##STR00105##
The 6-Chloro-3-ethylsulfanyl-quinoline-2-carboxylic acid was
synthesised using a similar protocol as described for the
Intermediate 7 (Step C): .sup.1H NMR (300 MHz, DMSO) ppm 13.72
(broad s, 1H); 8.40 (s, 1H); 8.13 (d, 1H); 8.04 (d, 1H); 7.75 (dd,
1H); 3.09 (q, 2H); 1.31 (t, 3H).
Intermediate 7: Synthesis of
6-bromo-3-ethylsulfanyl-quinoline-2-carboxylic acid
##STR00106##
Step A: ethyl 3-amino-6-bromo-quinoline-2-carboxylate
##STR00107##
To a mixture of pyridine (415 mg, 0.40 mL, 5.25 mmol) in 14.5 mL of
EtOH was slowly added ethyl bromopyruvate (1084 mg, 0.69 mL, 5
mmol) in EtOH (10 mL) dropwise over 30 min. The resulting mixture
was heated at 60-70.degree. C. for one hour and cooled to ambient
temperature. 5-Bromo-2-aminobenzaldehyde (990 mg, 4.95 mmol, 1 eq.)
and pyridine (1 mL) were added and after heating at reflux for 5 h,
pyrrolidine (838 mg, 1.0 mL, 11.78 mmol, 2.38 eq.) was added. The
resulting mixture was heated for an additional 2 h at reflux. The
reaction mixture was concentrated and the residue was
chromatographed (ethyl acetate/hexanes 1:3) to give the desired
product (719 mg, 49% yield). .sup.1H NMR (300 MHz, CDCl3) ppm 7.91
(d, 1H); 774 (d, 1H); 7.48 (dd, 1H); 7.25 (d, 1H); 5.67 (broad s,
2H); 4.55 (q, 2H); 1.53 (t, 3H).
Step B: ethyl 6-bromo-3-ethylsulfanyl-quinoline-2-carboxylate
##STR00108##
The ethyl 6-bromo-3-ethylsulfanyl-quinoline-2-carboxylate was
synthesised using a similar protocol as described for the
intermediate 1 (step A) and used without extra purification:
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 8.01 (d, 1H), 7.93 (d, 1H),
7.73 (dd, 1H), 4.55 (q, 2H), 3.03 (q, 2H); 1.39-1.51 (m, 6H).
Step C: 6-bromo-3-ethylsulfanyl-quinoline-2-carboxylic acid
##STR00109##
To stirred solution of compound ethyl
6-bromo-3-ethylsulfanyl-quinoline-2-carboxylate (351 mg, 1.03 mmol)
in THF (6 ml) was added aqueous solution of NaOH (1 M, 2.1 mL; 2.1
eq.) and the reaction mixture was stirred at ambient temperature
for 4 hours. After completion of the reaction, the reaction mixture
was diluted with water (15 mL) and extracted with ethyl acetate
(2.times.15 mL). The water phase was then acidified to pH=4 by 1 M
HCl solution and extracted with ethyl acetate (3.times.20 ml).
Organic layer was dried over sodium sulfate, filtered and
concentrated under reduced pressure to give the title product (310
mg, 96% yield). .sup.1H NMR (300 MHz, DMSO) ppm 13.75 (broad s,
1H); 8.40 (s, 1H); 8.29 (d, 1H); 7.96 (d, 1H); 7.86. (dd, 1H); 3.09
(q, 2H); 1.310 (t, 3H).
Intermediate 8: Synthesis of
6-ethylsulfanyl-1-methyl-2-(trifluoromethyl)benzimidazole-5-carboxylic
acid
##STR00110##
Step A: Synthesis of 4-chloro-2-ethylsulfanyl-5-nitro-benzoic
acid
##STR00111##
To a solution of 4-chloro-2-fluoro-5-nitro-benzoic acid (20 g,
91.095 mmol, commercially available) in 1-Methyl-2-pyrrolidone (250
mL) at 90.degree. C. was added sodium t-butoxide (9.6302 g, 100.20
mmol). After 10 min ethylsulfanylsodium (9.366 g, 100.20 mmol) was
added.
The reaction was stirred at 90.degree. C. for two hours. The
conversion is complete, two products were formed. The reaction
mixture was poured into one liter of water and pH was acidified by
addition of hydrochloride acid conc. (37%) and precipitate was
formed. Filtration of the solid gave the mixture of two products.
Filtrate was allowed to stand. The solid was suspended in ethyl
ether and filtered. The solid (pure) was identified as the
bis-ethylsulfanyl product. The filtrate was concentration under
vacuum to give 4-chloro-2-ethylsulfanyl-5-nitro-benzoic acid (8.9
g, 34 mmol, 37% Yield). LC-MS (Method A): RT 1.00 (260, MH.sup.-)
(262, MH.sup.+).
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 13.84 (s, 1H) 8.52 (s, 1H);
7.6 (s, 1H); 3.09 (q, 2H); 1.3 (t, 3H).
Step B: Synthesis of
2-ethylsulfanyl-4-(methylamino)-5-nitro-benzoic acid
##STR00112##
To a solution of 4-chloro-2-ethylsulfanyl-5-nitro-benzoic acid (8.9
g, 34 mmol) in tetrahydrofuran (20 mL, 244 mmol) was added gently
methylamine (2 mol/L) in tetrahydrofuran (100 mL, 200 mmol). The
mixture was stirred overnight at ambient temperature. Only a few
conversions were observed. The suspension was transferred in an
autoclave, 30 mL of methylamine 2N was added, and the reaction was
stirred at 80.degree. C. for five hours. The reaction is not
complete and 20 mL more of 2N methylamine was added then the
reaction was stirred in an autoclave over week end. Reaction is
finished, and reaction mixture was concentrated under vacuum.
Solids were taken up in water and basified with sodium hydroxide 1
N, then extracted with ethyl acetate. The water phase was acidified
with hydrochloride acid conc. 37% and extracted with ethyl acetate.
All organic layers are combined and were dried on magnesium
sulfate, and concentrated on vacuum. The residue was then purified
by Flash Chromatography to give
2-ethylsulfanyl-4-(methylamino)-5-nitro-benzoic acid (3.95 g, 15.4
mmol, 45% Yield) as a yellow-brownish solid. LC-MS (Method A): RT
1.04 (257, MH.sup.+).
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 12.87 (s, 1H) 8.68 (s, 1H);
6.55 (s, 1H); 3.05 (s, 3H); 3.00 (q, 2H) 1.33 (t, 3H).
Step C: Synthesis of
6-ethylsulfanyl-1-methyl-2-(trifluoromethyl)benzimidazole-5-carboxylic
acid
##STR00113##
To a solution of 2-ethylsulfanyl-4-(methylamino)-5-nitro-benzoic
acid (0.300 g, 1.17 mmol) in 2,2,2-trifluoroacetic acid (10 mL, 129
mmol) at 0.degree. C., zinc (0.260 g, 3.98 mmol) was added and
cooling bath was removed. After 30 min, reduction is complete
according to LC/MS; a few cyclized product was observed. The brown
solution was then heated at 70.degree. C. to cyclize the di-amino
product. After one hour LC/MS showed completion of the cyclisation.
Reaction mixture was concentrated to the half, poured into water
and extracted with ethyl acetate. Organic phase was washed with
water and brine, dried over magnesium sulfate and concentrated
under vacuum.
Residue was purified by flash chromatography to give
6-ethylsulfanyl-1-methyl-2-(trifluoromethyl)benzimidazole-5-carboxylic
acid (0.14 g, 0.46 mmol, 39.3% Yield).
LC-MS (Method A): RT 1.06 (303, MH.sup.-) (305, MH.sup.+).
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 13.03 (s, 1H) 8.30 (s, 1H);
7.64 (s, 1H); 4.00 (s, 3H); 3.06 (q, 2H) 1.32 (t, 3H).
Intermediate 9: Preparation of methyl
5-bromo-3-ethylsulfanyl-pyridine-2-carboxylate
##STR00114##
To a solution of methyl 5-bromo-3-chloro-pyridine-2-carboxylate
(0.100 g, 0.399 mmol) (commercial product) in THF, stirred at
0.degree. C., was added sodium ethanolate (0.034 g, 0.399 mmol).
After 1 hour at that temperature, the ice bath was removed and
stirring was continued for 20 hours. The reaction mixture was then
poured onto water (15 ml) and extracted twice with EtOAc. The
combined organic phases were dried over sodium sulfate and the
solvent was removed in vacuo. The residue was submitted to flash
chromatography over silica gel and the selected fractions
evaporated to yield methyl
5-bromo-3-ethylsulfanyl-pyridine-2-carboxylate as a colorless
solid.
LCMS (method 1): 276, 278 (M+H); retention time: 0.92 min.
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. ppm: 8.46 (s, 1H); 7.79
(s, 1H); 4.00 (s, 3H); 2.94 (q, 2H); 1.42 (t, 3H).
Intermediate 10: Synthesis of
6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)imidazo[4,5-b]pyridine-5-carb-
oxylic acid
##STR00115##
Step A: Synthesis of methyl
5-[(2,4-dimethoxyphenyl)methylamino]-3-ethylsulfanyl-pyridine-2-carboxyla-
te
##STR00116##
Methyl 5-bromo-3-ethylsulfanyl-pyridine-2-carboxylate (Intermediate
9, 5 mmol, 1380.75 mg) was dissolved in dried toluene (35 ml) and
cesium carbonate (7.5 mmol) was then added. The mixture was
degassed with argon and then
tris(dibenzylideneacetone)dipalladium(0) (0.11 mmol),
2,2'-bis(diphenylphosphino)-1,1'-binaphtyle (0.2 mmol) and
2,4-Dimethoxybenzylamine (5 mmol) were added.
The mixture was stirred under argon at 105.degree. C. (bath). The
dark violet color of the mixture changed to pale yellow within a 15
min. After 20 h, the reaction was cooled and the solvent was
removed under reduced pressure. The residue was purified on 50 g of
silica gel, eluent 50% ethyl acetate in hexane, then ethyl
acetate.
.sup.1H NMR (300 MHz, CDCl.sub.3) .delta. ppm 7.84 (d, 1H); 7.15
(d, 1H); 6.68 (d, 1H); 6.49-6.42 (m, 2H); 4.63 (t, 1H); 4.32 (d,
2H); 3.93 (s, 3H); 3.84 (s, 3H); 3.80 (s, 3H); 2.83 (q, 2H); 1.36
(t, 3H).
Step B: Synthesis of methyl
5-amino-3-ethylsulfanyl-pyridine-2-carboxylate
##STR00117##
Methyl
5-[(2,4-dimethoxyphenyl)methylamino]-3-ethylsulfanyl-pyridine-2-ca-
rboxylate (3.31 mmol, 1.2 g) was dissolved in dichloromethane (20
ml) at ambient temperature and trifluoroacetic acid (3.31 mmol) was
then added. The orange-red solution was stirred at ambient
temperature for 5 h. The volatiles were removed under reduced
pressure. The residue was alkalized with saturated solution of
NaHCO3 and extracted with ethyl acetate. The organic phase was
separated, dried and concentrated. The residue was purified on 50 g
of silica gel, eluent ethyl acetate to give a pale orange solid.
(530 mg, 75%)
.sup.1H NMR (300 MHz, CDCl.sub.3) .delta. ppm 7.88 (d, 1H); 6.8 (d,
1H); 4.2 (s, 2H); 3.9 (s, 3H); 2.83 (q, 2H); 1.36 (t, 3H).
Step C: Synthesis of methyl
5-amino-6-bromo-3-ethylsulfanyl-pyridine-2-carboxylate
##STR00118##
Methyl 5-amino-3-ethylsulfanyl-pyridine-2-carboxylate (0.93 mmol)
was dissolved in acetic acid glacial (10 ml) and then anhydrous
sodium acetate (1.22 mmol) was added. Then bromine (0.93 mmol) was
added dropwise at ambient temperature. The orange mixture was
stirred at ambient temperature for 2 hours. TLC showed no more
starting material. The volatiles were removed under reduced
pressure and the residue was dissolved in ethyl acetate. The
organic phase was washed with sodium hydrogen carbonate solution
followed by sodium thiosulfate solution and finally with water. The
organic phase was dried and concentrated. The residue was purified
on 25 g of silica gel, eluent 50% ethyl acetate in hexane to give
white solid (250 mg, 92%).
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 6.83 (d, 1H); 4.57 (s, 2H);
3.93 (s, 3H); 2.85 (q, 2H); 1.39 (t, 3H).
Step D: Synthesis of methyl
6-bromo-3-ethylsulfanyl-5-[(2,2,2-trifluoroacetyl)amino]pyridine-2-carbox-
ylate
##STR00119##
Methyl 5-amino-6-bromo-3-ethylsulfanyl-pyridine-2-carboxylate (0.82
mmol) was dissolved in dried tetrahydrofuran (10 ml) at ambient
temperature under argon and sodium carbonate was then added
followed by trifluoroacetic anhydride (0.82 mmol). The suspension
was stirred at ambient temperature for 16 hours. The volatiles were
removed under reduced pressure and the residue was dissolved in
ethyl acetate. The solution was washed with water; the organic
phase was dried and concentrated. The residue was purified on 40 g
of silica gel, eluent hexane/ethyl acetate (2:1) to give a white
solid.
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 8.76 (s, 1H); 8.60 (s, 1H);
3.99 (s, 3H); 3.00 (q, 2H); 1.42 (t, 3H).
Step E: Synthesis of methyl
6-bromo-3-ethylsulfanyl-5-[methyl-(2,2,2-trifluoroacetyl)amino]pyridine-2-
-carboxylate
##STR00120##
Methyl
6-bromo-3-ethylsulfanyl-5-[(2,2,2-trifluoroacetyl)amino]pyridine-2-
-carboxylate (0.3 mmol, 116 mg) was dissolved in
N,N-Dimethylformamide (1.2 ml) at ambient temperature under argon.
Then potassium carbonate (0.72 mmol) was added followed by methyl
iodine (0.3 mmol). The mixture was stirred at ambient temperature
for 40 h, then diluted with water and extracted with ethyl acetate.
The organic phase was washed with water, dried and concentrated.
The residue was purified on 15 g of silica gel, eluent
dichloromethane to give a white solid.
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 7.56 (s, 1H); 4.00 (s, 3H);
3.35 (s, 3H) 2.92 (q, 2H); 1.42 (t, 3H).
Step F: Synthesis of methyl
6-bromo-3-ethylsulfonyl-5-[methyl-(2,2,2-trifluoroacetyl)amino]pyridine-2-
-carboxylate
##STR00121##
To a solution of Methyl
6-bromo-3-ethylsulfanyl-5-[methyl-(2,2,2-trifluoroacetyl)amino]pyridine-2-
-carboxylate (200 mg) in dichloromethane (7 mL) was added
meta-chloroperbenzoic acid (253 mg). The yellow solution was
stirred at ambient temperature for an hour. After this time, the
reaction mixture was diluted with aqueous sodium thiosulfate
solution and extracted with dichloromethane, the combined organic
fractions washed with sodium carbonate, dried over magnesium
sulfate, and concentrated in vacuum. The crude product was purified
with silica gel, eluent 50% of ethyl acetate in hexane to give
colorless resin.
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 8.24 (d, 1H); 4.06 (s, 3H);
3.70 (q, 2H); 3.5 (s, 3H); 1.35 (t, 3H).
Step G: Synthesis of methyl
6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)imidazo[4,5-b]pyridine-5-carb-
oxylate
##STR00122##
To a solution of methyl
6-bromo-3-ethylsulfonyl-5-[methyl-(2,2,2-trifluoroacetyl)amino]pyridine-2-
-carboxylate (160 mg, 0.37 mmol) in DMSO (8 ml) under argon, sodium
trinitride (52 mg, 0.77 mmol) followed by copper Iodide (75 mg,
0.38 mmol) were added. The stirred mixture was degassed with argon
and then N,N'-Dimethylethylenediamine (57.4 mg, 0.65 mmol) was
added. The mixture was vigorously stirred while heated at
120.degree. C. for 53 min. The cooled mixture was further stirred
with saturated solution of ammonium chloride (25 ml) and 25 ml of
ethyl acetate for 30 min. Then the mixture was diluted with ethyl
acetate (100 ml). The organic phase was washed with brine. The
organic phase was dried, concentrated and the residue was purified
on 10 g of silica gel, eluent 50% of ethyl acetate in hexane to
give a colorless resin (20 mg, 15.4%).
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 8.56 (s, 1H); 4.11 (s, 3H);
4.06 (s, 3H); 3.65 (q, 2H); 1.37 (t, 3H).
Step H: Synthesis of
6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)imidazo[4,5-b]pyridine-5-carb-
oxylic acid
##STR00123##
To a solution of methyl
6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)imidazo[4,5-b]pyridine-5-carb-
oxylate in tetrahydrofuran (10 ml) at ambient temperature was added
lithium hydroxide (26.46 mg, 0.63 mmol) followed by water (4 ml).
The mixture was stirred at ambient temperature overnight. Evolution
of reaction was followed by TLC, after a complete conversion of
starting material the solvent was evaporated and the residue was
dissolved in 30 ml of water. The solution was acidified with 1M
hydrochloride acid to pH=3. The acid was extracted 3.times.50 ml of
ethyl acetate. The collected extracts were dried and evaporated to
dryness affording a pale solid.
.sup.1H NMR (300 MHz, Acetone) ppm 8.86 (s, 1H); 4.31 (s, 3H); 3.63
(q, 2H); 1.29 (t, 3H).
Example P1: Preparation of
2-(3-ethylsulfanyl-2-naphthyl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]-
pyridine (A1, 1.001)
##STR00124##
Step A: Preparation of
3-ethylsulfanyl-N-[2-(methylamino)-5-(trifluoromethyl)-3-pyridyl]naphthal-
ene-2-carboxamide A1a
##STR00125##
To a stirred solution of compound 1 (0.54 g, 2.96 mmol) in pyridine
(7 ml) was added EDCI.HCl (0.68 g, 3.56 mmol) followed by the
addition of compound 2 (0.68 g, 3.56 mmol). The total reaction
mixture was stirred for 8 hours at 120.degree. C. The reaction was
monitored by TLC. After completion of the starting amine, reaction
mixture was poured into water and extracted with ethyl acetate
(25.times.2 mL). The combined organic layer was washed with water,
brine and dried over Na.sub.2SO.sub.4. Filtered, concentrated and
purified by column chromatography using hexane-ethyl acetate
(100-200 silica gel) to give the desired compound as a white solid
(amount: 360 mg; Yield=41%). .sup.1H NMR (400 MHz, DMSO-d.sub.6):
.delta. (ppm) 9.87 (s, 1H), 8.29 (s, 2H), 7.96 (m, 4H), 7.59 (m,
2H), 6.87 (s, 1H), 3.08 (q, 2H), 2.85 (s, 3H), 1.29 (t, 3H).
Compound A4a
3-ethylsulfanyl-N-[2-(methylamino)-5-(trifluoromethyl)-3-pyridyl]quinolin-
e-2-carboxamide) was prepared by the same method using
3-ethylsulfanylquinoline-2-carboxylic acid as starting
material.
.sup.1H NMR (400 MHz, CDCl.sub.3): .delta. (ppm) 9.83 (s, 1H), 8.35
(s, 1H), 8.05 (m, 2H), 7.92 (s, 1H), 7.79 (d, 1H), 7.70 (m, 1H),
7.63 (m, 1H), 5.16 (s, 1H), 3.09-3.02 (m, 5H), 1.47 (t, 3H).
Step B: Preparation of
2-(3-ethylsulfanyl-2-naphthyl)-3-methyl-6-(trifluromethyl)imidazo[4,5-b]p-
yridine (A1, 1.001)
##STR00126##
To a stirred solution of compound A1a (360 mg, 0.88 mmol) in xylene
(5 ml) was added tosic acid (506 mg, 2.67 mmol) and the total
reaction mixture was heated to 150.degree. C. for 16 h. Reaction
was monitored by TLC. After completion of the starting material,
reaction mixture was diluted with ethyl acetate and washed with
water (2.times.10 mL). Organic layer was dried over
Na.sub.2SO.sub.4. Filtered, concentrated and purified by column
chromatography using hexane-ethyl acetate (100-200 silica gel) to
give the desired compound as a white solid (amount: 243 mg;
Yield=71%). .sup.1H NMR (400 MHz, CDCl.sub.3): .delta. (ppm) 8.72
(s, 1H), 8.34 (s, 1H), 7.97 (s, 1H), 7.89 (s, 1H), 7.85 (m, 2H),
7.60 (m, 1H), 7.52 (m, 1H), 3.78 (s, 3H), 2.92 (q, 2H), 1.26 (t,
3H).
Compound A4 (1.004) from table A were prepared by the same method
using A4a (Step A) as starting material. .sup.1H NMR (400 MHz,
CDCl.sub.3): .delta. (ppm) 8.75 (s, 1H), 8.41 (s, 1H), 8.13-8.09
(m, 2H), 7.83 (d, 1H), 7.72 (m, 1H), 7.62 (m, 1H), 4.08 (s, 3H),
3.05 (q, 2H), 1.38 (t, 3H).
Example P2: Preparation of
2-(3-ethylsulfinyl-2-naphthyl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]-
pyridine (A2, 1.002)
##STR00127##
To a stirred solution of compound A1 (90 mg, 0.23 mmol) in
CH.sub.2Cl.sub.2 (2 ml) was added m-CPBA (44 mg, 0.25 mmol) at RT.
The reaction mixture was then stirred for 2 h. Reaction was
monitored by TLC. After completion of the starting, the reaction
mixture was quenched with saturated Na.sub.2S203, NaHCO.sub.3 and
extracted with CH.sub.2Cl.sub.2 (10.times.2 mL). CH.sub.2Cl.sub.2
layer was dried over Na2SO4. Filtered, concentrated and the crude
was triturated with pentane to give the desired compound as a white
solid (amount: 71 mg; Yield=76%). .sup.1H NMR (400 MHz,
CDCl.sub.3): .delta. (ppm) 8.80 (s, 1H), 8.70 (s, 1H), 8.32 (s,
1H), 8.11-8.08 (m, 2H), 7.99 (m, 1H), 7.71 (m, 2H), 3.92 (s, 3H),
3.37 (m, 1H), 2.91 (m, 1H), 1.27 (t, 3H).
Compound A5 (1.005) from table A were prepared by the same method
using A4 (1.004) as starting material. .sup.1H NMR (400 MHz,
CDCl.sub.3): .delta. (ppm) 9.11 (s, 1H), 8.78 (s, 1H), 8.37 (s,
1H), 8.25 (d, 1H), 8.07 (d, 1H), 7.90 (m, 1H), 7.74 (m, 1H), 4.5
(s, 3H), 3.73 (m, 1H), 3.07 (m, 1H), 1.47 (t, 3H).
Example P3: Preparation of
2-(3-ethylsulfonyl-2-naphthyl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-b]-
pyridine (A3, 1.003)
##STR00128##
To a stirred solution of compound A1 (90 mg, 0.23 mmol) in
CH.sub.2Cl.sub.2 (3 ml) was added m-CPBA (158 mg, 0.92 mmol) at
ambient temperature. The reaction mixture was then stirred for 2
hours. Reaction was monitored by TLC. After completion of the
starting, the reaction mixture was quenched with saturated
Na.sub.2S.sub.2O.sub.3 and NaHCO.sub.3 and extracted with
CH.sub.2Cl.sub.2 (20.times.2 ml). CH.sub.2Cl.sub.2 layer was dried
over Na.sub.2SO.sub.4. Filtered, concentrated and the crude was
triturated with pentane to give the desired compound as a white
solid (amount: 80 mg; Yield=82%). .sup.1H NMR (400 MHz,
CDCl.sub.3): .delta. (ppm) 8.75 (m, 2H), 8.29 (s, 1H), 8.14 (m,
1H), 8.03 (s, 1H), 7.98 (m, 1H), 7.79 (m, 2H), 3.74 (s, 3H), 3.45
(q, 2H), 1.26 (t, 3H).
In addition, compound A6 (1.006) from table A were prepared by the
same method using A4 (1.004) as starting material. .sup.1H NMR (400
MHz, CDCl.sub.3): .delta. (ppm) 9.08 (s, 1H), 8.77 (s, 1H), 8.32
(s, 1H), 8.25 (d, 1H), 8.13 (d, 1H), 8.02 (t, 1H), 7.84 (t, 1H),
3.93 (s, 3H), 3.87 (q, 2H), 1.39 (t, 3H).
Example P4: Preparation of
2-[6-ethylsulfonyl-2-(trifluoromethyl)-3H-benzimidazol-5-yl]-3-methyl-6-(-
trifluoromethyl)imidazo[4,5-c]pyridine A7,
2-[6-ethylsulfonyl-3-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-c]pyridine A8 and
2-[6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-c]pyridine A9
##STR00129##
Step A: Preparation of
3-ethylsulfonyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]aniline
##STR00130##
To a stirred solution of
2-(4-bromo-2-ethylsulfonyl-phenyl)-3-methyl-6-(trifluoromethyl)imidazo
[4,5-c]pyridine (Prepared as described in WO 2015/000715, 471.71
mg) in dimethyl sulfoxide (12 mL) was added cooper iodine (220.0
mg) and sodium azide (140 mg). The stirred mixture was degassed
with argon and then DMEDA (Dimethylethylenediamine, 164 mg) was
added. The mixture was heated at 110.degree. C. for 55 min., then
cooled and stirred with a saturated solution of ammonium chloride
for 30 min. Then the mixture was repeatedly extracted with ethyl
acetate. The combined organic phases were washed with water, dried,
concentrated under vacuum. The residue was subjected to column
chromatography over silica gel (60 g), eluting with ethyl acetate.
The selected fractions were evaporated to yield the title compound
(49% yield): .sup.1H NMR (300 MHz, acetone-D6) ppm 9.14 (s, 1H);
8.44 (d, 1H); 8.10 (d, 1H); 7.73 (d, 1H); 6.01 (brs, 2H); 3.93 (s,
3H); 3.79 (q, 2H); 1.27 (t, 3H).
Step B: Preparation of
5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyrid-
in-2-yl]aniline
##STR00131##
To a stirred solution of
3-ethylsulfonyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]aniline (99.94 mg) in acetic acid (3 mL) was added NIS (61.42 mg).
The solution was stirred at ambient temperature overnight. Then,
the solvent was removed under reduced pressure. The residue was
dissolved in ethyl acetate, washed with Na.sub.2CO.sub.3 solution
followed by water. The organic phase was dried, concentrated under
vacuum. The residue was subjected to column chromatography over
silica gel (15 g), eluting with ethyl acetate:hexane (1:1). The
selected fractions were evaporated to yield the title compound
(90.5% yield). .sup.1H NMR (300 MHz, CDCl.sub.3) ppm 8.91 (s, 1H);
8.06 (s, 1H); 7.79 (s, 1H); 7.43 (s, 1H); 4.79 (bs, 2H); 3.76 (s,
3H); 3.32 (q, 2H); 1.24 (t, 3H).
Step C: Preparation of
N-[5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]py-
ridin-2-yl]phenyl]-2,2,2-trifluoro-acetamide
##STR00132##
To a stirred solution of
5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyrid-
in-2-yl]aniline (387.8 mg) in dried THF (15 mL) was added Na2CO3
(128.1 mg) and trifluoroacetic anhydride (0.27 mL). The clear
colorless solution was stirred at ambient temperature for 24 h. The
volatiles were removed under reduced pressure. The residue was
treated with a saturated solution of Na.sub.2CO.sub.3 and then
extracted three times with ethyl acetate. The combinated organic
phases were washed with water, dried and concentrated affording a
white solid. The compound was used without extra purification in
the next step. .sup.1H NMR (300 MHz, CDCl.sub.3) ppm 9.00 (s, 1H);
8.95 (s, 1H); 8.55 (bs, 1H); 8.09-8.07 (m, 2H); 3.78 (s, 3H); 3.26
(q, 2H); 1.27 (t, 3H).
Step D: Preparation of
2-[6-ethylsulfonyl-2-(trifluoromethyl)-3H-benzimidazol-5-yl]-3-methyl-6-(-
trifluoromethyl)imidazo[4,5-c]pyridine A7
##STR00133##
To a stirred solution of
N-[5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]py-
ridin-2-yl]phenyl]-2,2,2-trifluoro-acetamide (260.7 mg) in dimethyl
sulfoxide (10 mL) was added cooper iodine (90 mg) and sodium azide
(60.0 mg). The stirred mixture was degassed with argon and then
DMEDA (Dimethylethylenediamine, 65.6 mg) was added. The mixture was
heated at 110.degree. C. for 55 min., then cooled and stirred with
a saturated solution of ammonium chloride for 30 min. Then the
mixture was repeatedly extracted with ethyl acetate. The combined
organic phases were washed with water, dried, concentrated under
vacuum. The residue was subjected to column chromatography over
silica gel (60 g), eluting with ethyl acetate. The selected
fractions were evaporated to yield the title compound (78% yield):
.sup.1H NMR (300 MHz, acetone d6) ppm 9.16 (s, 1H); 8.59 (s, 1H);
8.26 (s, 1H); 8.13 (s, 1H); 8.01 (s, 1H); 3.86 (s, 3H); 3.54 (m,
2H); 1.20 (t, 3H).
Step E: Preparation of
2-[6-ethylsulfonyl-3-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-c]pyridine A8 and
2-[6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-c]pyridine A9
##STR00134##
To a stirred solution of
2-[6-ethylsulfonyl-2-(trifluoromethyl)-3H-benzimidazol-5-yl]-3-methyl-6-(-
trifluoromethyl)imidazo[4,5-c]pyridine A7 (157.5 mg) in acetone (20
mL) was added K2CO3 (138 mg) and iodomethane (0.06 mL). The mixture
was stirred at ambient temperature for 17 h. The volatiles were
removed under reduced pressure. Then, the residue was dissolved in
ethyl acetate, washed with water, dried and concentrated under
vacuum. The residue was subjected to column chromatography over
silica gel (60 g), eluting with ethyl acetate:hexane (1:1). The
selected fractions were evaporated to yield
2-[6-ethylsulfonyl-3-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-
-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridine A8 (43% yield)
and
2-[6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-c]pyridine A9 (40% yield).
2-[6-ethylsulfonyl-3-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-c]pyridine A9: .sup.1H NMR (600
MHz, CDCl.sub.3) .delta. ppm 1.28 (t, 3H) 3.51 (br s, 2H) 3.74 (s,
3H) 4.17 (s, 3H) 8.05 (s, 1H) 8.12 (s, 1H) 8.44 (s, 1H) 8.97 (s,
1H).
2-[6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-c]pyridine A8: .sup.1H NMR (600
MHz, CDCl.sub.3) .delta. ppm 1.22 (t, 3H) 3.08-3.57 (m, 2H) 3.77
(s, 3H) 4.06 (s, 3H) 7.69 (s, 1H) 8.12 (s, 1H) 8.79 (s, 1H) 8.97
(s, 1H).
Example P4b: Alternative preparation of
2-[6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-c]pyridine A9
Step A: Preparation of
6-ethylsulfanyl-1-methyl-N-[5-(methylamino)-2-(trifluoromethyl)-4-pyridyl-
]-2-(trifluoromethyl)benzimidazole-5-carboxamide and
6-ethylsulfanyl-1-methyl-N-[5-(methylamino)-2-(trifluoromethyl)-4-pyridyl-
]-2-(trifluoromethyl)benzimidazole-5-carboxamide
##STR00135##
To a suspension of
6-ethylsulfanyl-1-methyl-2-(trifluoromethyl)benzimidazole-5-carboxylic
acid (138 mg, Prepared previously) in dichloromethane (5 ml) was
added one drop of N,N-dimethylformamide, followed by oxalyl
chloride (1.8 equiv., 0.103 mL). After the end of gas evolution,
the reaction mixture was in the form of a pale yellow solution. The
latter was evaporated under reduced pressure at a bath temperature
of 60.degree. C. The residue formed dark red crystals of
5-bromo-5-bromo-3-ethylsulfanyl-benzothiophene-2-carboxylic
chloride and the residue was redissolved in 6 ml of
tetrahydrofuran. To a solution of
N3-methyl-6-(trifluoromethyl)pyridine-3,4-diamine (85 mg,
commercially available CAS 1643139-91-6) in ethyl acetate (5 ml)
was added N,N-diethylethanamine (2.5 equiv., 0.157 mL) then the
resulting solution was cooled with an ice bath, before slow
addition of the previous acyl chloride solution. The resulting
mixture was stirred 1 hour at ambient temperature. The solution was
neutralized by addition of a saturated aqueous solution of sodium
bicarbonate and the product was extracted twice with ethyl acetate.
The organic solution was dried over sodium sulfate and evaporated
under reduced pressure to yield the crude product. A mixture of
6-ethylsulfanyl-1-methyl-N-[5-(methylamino)-2-(trifluoromethyl)-4-pyridyl-
]-2-(trifluoromethyl)benzimidazole-5-carboxamide and
6-ethylsulfanyl-1-methyl-N-[5-(methylamino)-2-(trifluoromethyl)-4-pyridyl-
]-2-(trifluoromethyl)benzimidazole-5-carboxamide was obtained after
column chromatography over silica gel, eluting with ethyl
acetate/cyclohexane and used without extra purification. LC-MS
(Method A): RT 0.95 (476, MH.sup.-) (478, MH.sup.+).
Step B: Preparation of
2-[6-ethylsulfanyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-c]pyridine A39
##STR00136##
A mixture of
6-ethylsulfanyl-1-methyl-N-[5-(methylamino)-2-(trifluoromethyl)-4-pyridyl-
]-2-(trifluoromethyl)benzimidazole-5-carboxamide and
6-ethylsulfanyl-1-methyl-N-[5-(methylamino)-2-(trifluoromethyl)-4-pyridyl-
]-2-(trifluoromethyl)benzimidazole-5-carboxamide (0.16 g) in acetic
acid (3.2 ml) was heated to 150.degree. C. for 1 hour in a
microwave. The reaction was monitored by TLC. After completion of
the starting material, reaction mixture was diluted with ethyl
acetate and washed with water. Organic layer was dried over sodium
thiosulfate. Filtered, concentrated and purified by column
chromatography using cyclohexane-ethyl acetate to give
2-[6-ethylsulfanyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3--
methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridine as a yellow solid
(96 mg; Yield=62%).
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. ppm 1.22 (t, 3H) 2.86 (q,
2H) 3.76 (s, 3H) 4.03 (s, 3H) 7.60 (s, 1H) 7.98 (s, 1H) 8.16 (s,
1H) 8.94 (s, 1H) LC-MS (Method A): RT 1.04 (461, MH.sup.+).
Step C: Preparation of
2-[6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-c]pyridine A9
##STR00137##
To a stirred solution of
2-[6-ethylsulfanyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-c]pyridine A39 (90 mg) in
CH.sub.2Cl.sub.2 (10 ml) was added acid 3-chloroperoxybenzoique
(2.05 equiv., 92 mg) at ambient temperature. The reaction mixture
was then stirred for 1 hour. The reaction was monitored by TLC.
After completion of the starting, the reaction mixture was quenched
with saturated sodium thiosulfate, sodium hydrogen carbonate and
extracted with dichloromethane (2 times). Organic layer was dried
over magnesium sulphate. Filtered, concentrated and the crude was
purified by column chromatography using cyclohexane-ethyl acetate
to give the desired compound as a white solid (97 mg;
Yield=100%).
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. ppm 1.28 (t, 3H) 3.51 (br
s, 2H) 3.74 (s, 3H) 4.17 (s, 3H) 8.05 (s, 1H) 8.12 (s, 1H) 8.44 (s,
1H) 8.97 (s, 1H). LC-MS (Method A): RT 0.97 (492, MH.sup.+).
Example P5: Preparation of
2-(6-ethylsulfonyl-3-methyl-benzimidazol-5-yl)-3-methyl-6-(trifluoromethy-
l)imidazo[4,5-c]pyridine A11 and
2-(6-ethylsulfonyl-1-methyl-benzimidazol-5-yl)-3-methyl-6-(trifluoromethy-
l)imidazo[4,5-c]pyridine A12
##STR00138##
Step A: Preparation of
N-[5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]py-
ridin-2-yl]phenyl]formamide
##STR00139##
A stirred solution of
5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyrid-
in-2-yl]aniline (199 mg) in dried formic acid (5.89 mL) was
refluxed for 17 hours. Then the solvent was removed under reduced
pressure and the residue was dissolved in ethyl acetate and washed
with a solution of Na.sub.2CO.sub.3. The organic phase was
separated, washed with water and dried. Evaporation of the solvent
afforded a solid (86% yield) used in the next step without
extra-purification. .sup.1H NMR (300 MHz, acetone--D6) ppm 9.25
(bs, 1H); 9.15 (s, 1H); 9.10 (s, 1H); 8.70 (bs, 1H); 8.40 (s, 1H);
8.12 (s, 1 h); 3.89 (s, 3H); 3.49 (q, 2H); 1.22 (t, 3H).
Step B: Preparation of
N-[2-amino-5-ethylsulfonyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]p-
yridin-2-yl]phenyl]formamide
##STR00140##
A similar protocol described in Example P4, step D was use but, the
no cyclized compound was obtained (50% yield).
N-[2-amino-5-ethylsulfonyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]p-
yridin-2-yl]phenyl]formamide. The compound was used without extra
purification in the next step. .sup.1H NMR (300 MHz, CDCl3) ppm
8.93 (s, 1H); 8.45 (s, 1H); 8.08 (s, 1H); 7.92-7.86 (m, 1H); 7.68
(bs, 1H); 6.86 (s, 1H); 4.74 (bs, 2H); 3.77 (s, 3H); 3.27 (q, 2H);
1.23 (t, 3H).
Step C:
2-(6-ethylsulfonyl-1H-benzimidazol-5-yl)-3-methyl-6-(trifluorometh-
yl)imidazo[4,5-c]pyridine A10
##STR00141##
A stirred solution of
N-[2-amino-5-ethylsulfonyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]p-
yridin-2-yl]phenyl]formamide (59.84 mg) in acetic acid (5 mL) was
refluxed for 17 h. The solvent was then removed under reduced
pressure. The residue was dissolved in ethyl acetate and washed
with an excess of saturated solution of Na.sub.2CO.sub.3. The
organic phase was separated, dried and concentrated under vacuum.
The residue was subjected to column chromatography over silica gel
(15 g), eluting with ethyl acetate:methanol (9:1). The selected
fractions were evaporated to yield
2-(6-ethylsulfonyl-1H-benzimidazol-5-yl)-3-methyl-6-(trifluoromethyl)imid-
azo[4,5-c]pyridine A10. .sup.1H NMR (300 MHz, acetone d 6) ppm 9.14
(s, 1H); 8.60 (s, 1H); 8.48 (s, 1H); 8.12 (s, 1H); 8.08 (s, 1H);
3.84 (s, 3H); 3.50 (m, 2H); 1.17 (t, 3H).
Step D: Preparation of
2-(6-ethylsulfonyl-3-methyl-benzimidazol-5-yl)-3-methyl-6-(trifluoromethy-
l)imidazo[4,5-c]pyridine A11 and
2-(6-ethylsulfonyl-1-methyl-benzimidazol-5-yl)-3-methyl-6-(trifluoromethy-
l)imidazo[4,5-c]pyridine A12
##STR00142##
A similar protocol described in Example P4, step E. The compounds
were not separable on silica gel but, were separable on HPLC
chiral.
Preparative HPLC Method:
Auto purification System from Waters: 2767 sample Manager, 2489
UV/Visible Detector, 2545 Quaternary Gradient Module.
Column: Daicel CHIRALPAK.RTM. IC, 50 m, 1.0 cm.times.25 cm
Mobile phase: Hept/EtOAc/DEA 60/40/0.1%
Flow rate: 10 ml/min
Detection: UV 230 nm
Sample concentration: 23 mg/mL in EtOAc/DCM/MeOH
Injection: 200-600 .mu.l
TABLE-US-00015 First eluting Peak Second eluting Peak Retention
time (min) ~0.89 Retention time (min) ~1.39 Quantity (mg) return
fraction Quantity (mg) return fraction Chemical purity (area % at
265 Chemical purity (area % at 265 nm) 99 nm) 99
2-(6-ethylsulfonyl-3-methyl-benzimidazol-5-yl)-3-methyl-6-(trifluoromethy-
l)imidazo[4,5-c]pyridine A11 (Peak 2): .sup.1H NMR (400 MHz,
CDCl.sub.3) ppm 8.94 (s, 1H); 8.68 (s, 1H); 8.19 (s, 1H); 8.10 (s,
1H); 7.59 (s, 1H); 3.96 (s, 3H); 3.75 (s, 3H); 3.42-3.20 (m, 2H);
1.22 (t, 3H).
2-(6-ethylsulfonyl-1-methyl-benzimidazol-5-yl)-3-methyl-6-(trifluoromethy-
l)imidazo[4,5-c]pyridine A12 (peak 1): .sup.1H NMR (400 MHz,
CDCl.sub.3) ppm 8.95 (s, 1H); 8.34 (s, 1H); 8.22 (s, 1H); 8.10 (s,
1H); 7.95 (s, 1H); 4.06 (s, 3H); 3.73 (s, 3H); 3.48 (m, 2H); 1.26
(t, 3H).
Example P6: Preparation of
2-(6-ethylsulfonyl-2-methyl-3H-benzimidazol-5-yl)-3-methyl-6-(trifluorome-
thyl)imidazo[4,5-c]pyridine A13,
2-(6-ethylsulfonyl-2,3-dimethyl-benzimidazol-5-yl)-3-methyl-6-(trifluorom-
ethyl)imidazo[4,5-c]pyridine A14 and
2-(6-ethylsulfonyl-1,2-dimethyl-benzimidazol-5-yl)-3-methyl-6-(trifluorom-
ethyl)imidazo[4,5-c]pyridine A15
##STR00143##
Step A: Preparation of
N-[5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]py-
ridin-2-yl]phenyl]acetamide
##STR00144##
To a stirred solution of
5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyrid-
in-2-yl]aniline (209.1 mg) in toluene (5. mL) was added pyridine
(0.07 mL), acetyl chloride (0.06 mL). The reaction was refluxed for
7 hours. Then the volatiles were removed under reduced pressure and
the residue was dissolved in ethyl acetate and washed with 0.1.M
HCl, then with water, dried and concentrated under vacuum. The
residue was subjected to column chromatography over silica gel (25
g), eluting with ethyl acetate. The selected fractions were
evaporated to yield the
N-[5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]py-
ridin-2-yl]phenyl]acetamide (82% yield). .sup.1H NMR (300 MHz,
CDCl.sub.3) ppm 9.07 (s, 1H); 8.93 (s, 1H); 8.08 (s, 1H); 7.98 (s,
1H); 7.68 (bs, 1H); 3.77 (s, 3H); 3.30 (q, 2H); 2.35 (s, 3H); 1.26
(t, 3H).
Step B: Preparation of
N-[2-amino-5-ethylsulfonyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]p-
yridin-2-yl]phenyl]acetamide
##STR00145##
A protocol identical to example P5, step B was used. Analytic data
of the title compound: .sup.1H NMR (300 MHz, CDCl3) ppm 8.91 (s,
1H); 8.40 (s, 1H); 8.07 (s, 1H); 7.93 (s, 1H); 6.81 (s, 1H); 4.86
(bs, 2H); 3.75 (s, 3H); 3.24 (q, 2H); 2.28 (s, 3H); 1.24 (t,
3H).
Step C: Preparation of
2-(6-ethylsulfonyl-2-methyl-3H-benzimidazol-5-yl)-3-methyl-6-(trifluorome-
thyl)imidazo[4,5-c]pyridine A13
##STR00146##
A protocol identical to example P5, step C was used. The compound
obtained was used without extra purification in the next step.
Step D: Preparation of
2-(6-ethylsulfonyl-2,3-dimethyl-benzimidazol-5-yl)-3-methyl-6-(trifluorom-
ethyl)imidazo[4,5-c]pyridine A14 and
2-(6-ethylsulfonyl-1,2-dimethyl-benzimidazol-5-yl)-3-methyl-6-(trifluorom-
ethyl)imidazo[4,5-c]pyridine A15
##STR00147##
A similar protocol described in Example P4, step E. The compounds
were not separable on silica gel. A mixture of
2-(6-ethylsulfonyl-2,3-dimethyl-benzimidazol-5-yl)-3-methyl-6-(trifluorom-
ethyl)imidazo[4,5-c]pyridine A14 and
2-(6-ethylsulfonyl-1,2-dimethyl-benzimidazol-5-yl)-3-methyl-6-(trifluorom-
ethyl)imidazo[4,5-c]pyridine A15 was obtained in 89% yield. Then,
they were separable on HPLC chiral.
Preparative HPLC Method:
Auto purification System from Waters: 2767 sample Manager, 2489
UV/Visible Detector, 2545 Quaternary Gradient Module.
Column: Daicel CHIRALPAK.RTM. IC, 5 .mu.m, 1.0 cm.times.25 cm
Mobile phase: Hept/EtOAc/DEA 50/50/0.1%
Flow rate: 10 ml/min
Detection: UV 230 nm
Sample concentration: 15 mg/mL in EtOAc/DCM/MeOH
Injection: 400-800 .mu.l
TABLE-US-00016 First eluting Peak Second eluting Peak Retention
time (min) ~0.74 Retention time (min) ~1.39 Quantity (mg) return
fraction Quantity (mg) return fraction Chemical purity (area % at
265 Chemical purity (area % at 265 nm) 99 nm) 98
2-(6-ethylsulfonyl-2,3-dimethyl-benzimidazol-5-yl)-3-methyl-6-(trifluorom-
ethyl)imidazo[4,5-c]pyridine A14 (peak 2): .sup.1H NMR (400 MHz,
CDCl.sub.3) ppm 8.95 (s, 1H); 8.53 (s, 1H); 8.10 (s, 1H); 7.46 (s,
1H); 3.83 (s, 3H); 3.76 (s, 3H); 3.32 (m, 2H); 2.74 (s, 3H); 1.20
(t, 3H).
2-(6-ethylsulfonyl-1,2-dimethyl-benzimidazol-5-yl)-3-methyl-6-(trifluorom-
ethyl)imidazo[4,5-c]pyridine A15 (peak 1): .sup.1H NMR (400 MHz,
CDCl.sub.3) ppm 8.95 (s, 1H); 8.21 (s, 1H); 8.10 (s, 1H); 7.79 (s,
1H); 3.93 (s, 3H); 3.72 (s, 3H); 3.46 (m, 2H); 2.75 (s, 3H); 1.25
(t, 3H).
2-(6-ethylsulfonyl-2-phenyl-3H-benzimidazol-5-yl)-3-methyl-6-(trifluorome-
thyl)imidazo[4,5-c]pyridine A16 was prepared using the same serial
of step described in Example P6, step A to step C.
##STR00148##
LC-MS (method A) RT 0.95, 486 (MH.sup.+), 484 (M-H.sup.+).
Example P7: Preparation of
2-(6-ethylsulfonyl-3H-benzotriazol-5-yl)-3-methyl-6-(trifluoromethyl)imid-
azo[4,5-c]pyridine A17
##STR00149##
Step A: Preparation of
4-ethylsulfonyl-5-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]benzene-1,2-diamine
##STR00150##
To a stirred solution of
N-[2-amino-5-ethylsulfonyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]p-
yridin-2-yl]phenyl]formamide (Prepared in example P5, step B, 90
mg) in methanol (7 mL) was added water (1 mL) and sodium hydroxide
(20 mg) at ambient temperature. The mixture was refluxed for 17
hours. The solvent was evaporated and the residue was dissolved in
ethyl acetate. The organic phase was washed with water, dried and
concentrated under vacuum. The residue was subjected to column
chromatography over silica gel (10 g), eluting with 10% MeOH in
ethyl acetate. The selected fractions were evaporated to yield the
4-ethylsulfonyl-5-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]benzene-1,2-diamine (60% yield). .sup.1H NMR (300 MHz, CDCl.sub.3)
ppm 8.89 (s, 1H); 8.06 (d, 1H); 7.45 (s, 1H); 6.74 (s, 1H); 3.97
(brs, 2H); 3.74 (s, 3H); 3.23 (q, 2H); 1.21 (t, 3H).
Step B: Preparation of
2-(6-ethylsulfonyl-3H-benzotriazol-5-yl)-3-methyl-6-(trifluoromethyl)imid-
azo[4,5-c]pyridine A17
##STR00151##
To a stirred solution of
4-ethylsulfonyl-5-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]benzene-1,2-diamine (80 mg) in acetic acid (3 mL) was added a
solution of sodium nitrite (69 mg) in water (1 mL) at ambient
temperature. The mixture was stirred at ambient temperature for 2
h. Then, the solvents were evaporated under reduced pressure and
the residue was dissolved into ethyl acetate and water. The organic
phase was separated and washed with a saturated solution of
Na.sub.2CO.sub.3, dried and concentrated under vacuum. The residue
was subjected to column chromatography over silica gel (30 g),
eluting with 10% MeOH in ethyl acetate. The selected fractions were
evaporated to yield the
2-(6-ethylsulfonyl-3H-benzotriazol-5-yl)-3-methyl-6-(trifluoromethyl)imid-
azo[4,5-c]pyridine A17 (73% yield). .sup.1H NMR (300 MHz,
acetone-D6) ppm 9.18 (s, 1H); 8.82 (s, 1H); 8.47 (s, 1H); 8.15 (s,
1H); 3.88 (s, 3H); 3.59 (q, 2H); 1.21 (t, 3H).
Example P8: Preparation of
5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]-2,1,3-benzothiadiazole A18
##STR00152##
To a stirred solution of
4-ethylsulfonyl-5-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]benzene-1,2-diamine (prepared in example P7, step A, 99.85 mg) in
dried toluene (10 mL) was added thionyl chloride (0.06 mL). The
mixture refluxed under argon for 2 h. Then the solvent was
evaporated and the residue was dissolved in ethyl acetate. The
organic phase was washed with a saturated solution NaHCO.sub.3,
dried and concentrated under vacuum. The residue was subjected to
column chromatography over silica gel (10 g), eluting with hexane:
ethyl acetate (1:1). The selected fractions were evaporated to
yield the
5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]-2,1,3-benzothiadiazole A18 (47% yield). .sup.1H NMR (300 MHz,
CDCl.sub.3) ppm 8.99 (s, 2H); 8.26 (s, 1H); 8.13 (s, 1H); 3.83 (s,
3H); 3.50 (q, 2H); 1.30 (t, 3H).
Example P9: Preparation of
5-ethylsulfonyl-2-methyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyr-
idin-2-yl]-1,3-benzothiazole A19
##STR00153##
To a stirred solution of
N-[5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]py-
ridin-2-yl]phenyl]acetamide (prepared in example P6, step A, 171.22
mg) in dried toluene (7 mL) was added the lawesson reagent (76.85
mg). The mixture refluxed under argon for 17 h. Then the solvent
was evaporated and The residue was subjected to column
chromatography over silica gel (35 g), eluting with ethyl acetate.
The selected fractions were evaporated to yield the
5-ethylsulfonyl-2-methyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyr-
idin-2-yl]-1,3-benzothiazole A19 (80.5% yield). .sup.1H NMR (300
MHz, CDCl3) ppm 8.96 (s, 1H); 8.77 (s, 1H); 8.10 (s, 1H); 8.02 (s,
1H); 3.77 (s, 3H); 3.37 (q, 2H); 2.98 (s, 3H); 1.25 (t, 3H).
Example P10: Preparation of
6-ethylsulfonyl-7-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]quinoxaline A20
##STR00154##
To a stirred solution of
4-ethylsulfonyl-5-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]benzene-1,2-diamine (prepared in example P7, step A, 171.22 mg) in
ethanol (5 mL) was added of a solution of glyoxal (40% in aqueous
water). The mixture refluxed under argon for 1 h. Then the solvent
was evaporated and The residue was triturated with 5 mL of cold
methanol. The solid was isolated by filtration, washed with a
little cold methanol and dried to give
6-ethylsulfonyl-7-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-
-2-yl]quinoxaline A20 (38% yield). .sup.1H NMR (300 MHz,
CDCl.sub.3) ppm 9.15 (s, 1H); 9.12 (s, 1H); 9.05 (s, 1H); 9.00 (s,
1H); 8.34 (s, 1H); 8.13 (s, 1H); 3.83 (s, 3H); 3.53 (q, 2H); 1.31
(t, 3H).
Compounds A28 and A29 were prepared using the protocol described
before, and with the Trifluoro methyl glyoxal (20% aq. soln).
Compounds A28 and A29 were purified on 30 g of silica gel, eluent
hexane:ethyl acetate 1:1.
A28: .sup.1H NMR (600 MHz, CDCl.sub.3) .delta. ppm 1.34 (t, 3H),
3.56 (m, 2H), 3.85 (s, 3H), 8.16 (s, 1H), 8.47 (s, 1H), 9.03 (s,
1H), 9.15 (s, 1H), 9.47 (s, 1H).
A29: .sup.1H NMR (600 MHz, CDCl.sub.3) .delta. ppm 1.33 (t, 3H),
3.53 (m, 2H), 3.85 (s, 3H), 8.16 (s, 1H), 8.46 (s, 1H), 9.03 (s,
1H), 9.18 (s, 1H), 9.44 (s, 1H).
Example P11: Preparation of
3-ethylsulfanyl-2-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]quinolone A21,
3-ethylsulfonyl-2-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]quinolone A22,
2-(3-ethylsulfanyl-2-naphthyl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]-
pyridine A23 and
2-(3-ethylsulfonyl-2-naphthyl)-3-methyl-6-(trifluoromethyl)imidazo[4,5-c]-
pyridine A24
Compounds A21 and A23 were prepared using intermediate 1 or 2 with
the protocol described in Example P1, and with the diamide A (see
scheme, prepared in WO 2015/000715), then A22 and A24 were prepared
via the oxidation of A21 and A23 via an identical method as
described in Example P3.
##STR00155## Compound A21:
##STR00156##
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 9.05 (s, 1H), 8.28 (s, 1H),
8.20 (s, 1H), 8.16 (d, 1H), 7.89 (d, 1H), 7.79 (m, 1H), 7.70 (m,
1H), 4.14 (s, 3H), 3.10 (q, 2H), 1.42 (t, 3H).
Compound A22:
##STR00157##
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 9.12 (s, 1H), 9.04 (s, 1H),
8.30 (d, 1H), 8.17 (m, 2H), 8.07 (t, 1H), 7.90 (t, 1H), 3.99 (s,
3H), 3.88 (q, 2H), 1.42 (t, 3H).
Compound A23:
##STR00158##
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 8.95 (s, 1H), 8.16 (s, 1H),
8.00 (s, 1H), 7.92 (s, 1H), 7.87 (d, 1H), 7.63 (t, 1H), 7.55 (m,
1H), 7.70 (m, 1H), 3.82 (s, 3H), 2.92 (q, 2H), 1.26 (t, 3H).
Compound A24:
##STR00159##
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 8.96 (s, 1H), 8.77 (s, 1H),
8.16 (m, 1H), 8.12 (s, 1H), 8.05 (s, 1H), 8.01 (m, 1H), 7.82 (m,
2H), 3.78 (s, 3H), 3.42 (m, 2H), 1.26 (t, 3H).
Example P12: Preparation of
7-ethylsulfanyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]isoquinoline A25,
7-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]isoquinoline A26,
7-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]-2-oxido-isoquinolin-2-ium A27
Compounds A25 was prepared using intermediate 3 with the protocol
described in P1, then A26 and A27 were prepared via the oxidation
of A25 via an identical method as described in Example P3, in the
case of A27, 2.5 eq of m-CPBA were used.
Compound A25:
##STR00160##
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 9.32 (s, 1H), 8.98 (s, 1H),
8.61 (d, 1H), 8.17 (s, 1H), 7.99 (s, 2H), 7.68 (d, 1H), 3.84 (s,
3H), 3.00 (q, 2H), 1.32 (t, 3H).
Compound A26:
##STR00161##
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 9.60 (s, 1H), 8.98 (s, 1H),
8.93 (s, 1H), 8.89 (d, 1H), 8.12 (s, 1H), 8.06 (s, 1H), 7.83 (d,
1H), 3.80 (s, 3H), 3.44 (br. s., 2H), 1.28 (t, 3H).
Compound A27:
##STR00162##
.sup.1H NMR (300 MHz, CDCl.sub.3) ppm 8.97 (d, 2H), 8.59 (s, 1H),
8.36 (dd, 1H), 8.12 (s, 1H), 7.98 (s, 1H), 7.82 (d, 1H), 3.80 (s,
3H), 3.44 (m, 2H), 1.28 (t, 3H).
Example P13: Preparation of
5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]-1,3-benzothiazole A30
##STR00163##
Step A: Preparation of
N-[5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]py-
ridin-2-yl]phenyl]thioformamide
##STR00164##
To a stirred solution of
N-[5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]py-
ridin-2-yl]phenyl]formamide (102.3 mg, prepared in example P5, Step
A) in dried toluene (8 mL) was added the lawesson reagent (50 mg).
The mixture refluxed under argon for 15 minutes. Then the solvent
was concentrated to 2 ml solution and the residue was subjected to
column chromatography over silica gel (20 g), eluting with
hexane/ethyl acetate 1:1. The selected fractions were evaporated to
yield the
N-[5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]py-
ridin-2-yl]phenyl]thioformamide (80 mg). H NMR (300 MHz, DMSO)
.delta. ppm 12.02 (s, 1H); 9.85-9.77 (m, 1H); 9.26 (s, 1H);
8.55-7.92 (m, 3H); 3.77 (s, 3H); 3.51 (q, 2H); 1.17 (t, 3H).
Step B: Preparation of
5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]-1,3-benzothiazole A30
##STR00165##
N-[5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]py-
ridin-2-yl]phenyl]thioformamide (89 mg) was suspended in
Dimethoxyethane (7 mL) under argon and cesium carbonate (78.24 mg),
copper iodine (3.8 mg) and 1,10-Phenanthroline (7.2 mg) were added.
The mixture was refluxed under argon for 17 h. The solvent was
evaporated under reduced pressure and the residue was subjected to
column chromatography over silica gel (25 g), eluting with ethyl
acetate. The selected fractions were evaporated to yield the
5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]-1,3-benzothiazole A30 (68 mg). .sup.1H NMR (300 MHz, CDCl.sub.3)
.delta. ppm 9.35 (s, 1H); 8.99 (s, 1H); 8.97 (s, 1H); 8.19 (s, 1H);
8.11 (s, 1H); 3.78 (s, 3H); 3.39 (m, 2H); 1.27 (t, 3H).
Example P14: Preparation of
5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]-2-(trifluoromethyl)-1,3-benzothiazole A31
##STR00166##
Compound A31 was prepared using the protocol described in Example
P9, using as starting material
N-[5-ethylsulfonyl-2-iodo-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]py-
ridin-2-yl]phenyl]-2,2,2-trifluoro-acetamide (Example P4, Step C).
.sup.1H NMR (300 MHz, CDCl.sub.3) .delta. ppm 9.07 (s, 1H); 8.98
(s, 1H); 8.24 (s, 1H); 8.12 (s, 1H); 3.78 (s, 3H); 3.41 (q, 2H);
1.26 (t, 3H).
Example P15: Preparation of
6-ethylsulfonyl-5-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]-2-(trifluoromethyl)-1H-imidazo[4,5-b]pyridine A34,
6-ethylsulfonyl-1-methyl-5-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyr-
idin-2-yl]-2-(trifluoromethyl)imidazo[4,5-b]pyridine A33 and
6-ethylsulfonyl-3-methyl-5-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyr-
idin-2-yl]-2-(trifluoromethyl)imidazo[4,5-b]pyridine A32
##STR00167##
Compounds A34, A33 and A32 were prepared as described in Example P4
using same conditions with, as starting material, the
2-(5-bromo-3-ethylsulfonyl-2-pyridyl)-3-methyl-6-(trifluoromethyl)imidazo-
[4,5-c]pyridine (C1, prepared as described in WO 2015/000715) and
replacing NIS by NBS in step B as described in the following
scheme
##STR00168## ##STR00169##
C2: .sup.1H NMR (300 MHz, acetone-d6) .delta. ppm 9.14 (s, 1H);
8.44 (d, 1H); 8.10 (d, 1H); 7.73 (d, 1H); 6.01 (brs, 2H); 3.93 (s,
3H); 3.79 (q, 2H); 1.27 (t, 3H).
C3: .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. ppm 8.94 (s, 1H);
8.07 (d, 1H); 7.71 (s, 1H) 3.90 (s, 3H); 3.78 (q, 2H); 1.36 (t,
3H).
C4: .sup.1H NMR (300 MHz, acetone-d6) .delta. ppm 9.18 (s, 1H);
9.13 (s, 1H); 8.13 (d, 1H); 3.99 (s, 3H); 3.76 (q, 2H); 1.29 (t,
3H).
C5: .sup.1H NMR (300 MHz, acetone-d6) .delta. ppm 10.10 (bs, 1H);
9.18 (s, 1H); 8.27 (s, 1H); 8.14 (s, 1H); 6.98 (bs, 2H); 3.98 (s,
3H); 3.65 (q, 2H); 1.25 (t, 3H).
A34: .sup.1H NMR (300 MHz, acetone-d6) .delta. ppm 9.15 (s, 1H);
8.54 (s, 1H); 8.11 (s, 1H); 3.88 (s, 3H); 3.69 (q, 2H); 1.24 (t,
3H).
A33: .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. ppm 9.00 (s, 1H);
8.77 (s, 1H); 8.11 (s, 1H); 4.19 (s, 3H); 3.94 (m, 5H); 1.40 (t,
3H).
A32: .sup.1H NMR (300 MHz, CDCl.sub.3) .delta. ppm 9.02 (s, 2H);
8.13 (s, 1H); 4.12 (s, 3H); 3.87 (s, 3H); 3.70 (q, 2H); 1.35 (t,
3H).
Example P16: Preparation of
5-ethylsulfonyl-1-methyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyr-
idin-2-yl]benzotriazole A35,
6-ethylsulfonyl-1-methyl-5-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyr-
idin-2-yl]benzotriazole A36 and
5-ethylsulfonyl-2-methyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyr-
idin-2-yl]benzotriazole A37
##STR00170##
A similar protocol described in Example P4, step E starting from
2-(6-ethylsulfonyl-3H-benzotriazol-5-yl)-3-methyl-6-(trifluoromethyl)imid-
azo[4,5-c]pyridine A17. The compounds A36 and A37 were not
separable on silica gel and were separate by HPLC on reverse phase
using the following method:
Autopurification System from Waters: 2767 sample Manager, 2489
UV/Visible Detector, 2545 Quaternary Gradient Module. Column:
Phenomenex Gemini NX C18, 4 micron particle size, 80 Angstrom,
75.times.30.00 mm, DAD Wavelength (nm): 220 and 254. Solvent
Gradient: Reversed Phase, A=water (in House-HPLC quality) and
B=Acetonitrile for prep. HPLC.
TABLE-US-00017 Time A % B % Flow (ml/min) 0.00 70 30 50.00 0.01 70
30 50.00 6.00 30 70 50.00 7.90 30 70 50.00 8.00 0 100 50.00 8.90 0
100 50.00 9.00 70 30 50.00 10.0 70 30 50.00
A35: .sup.1H NMR (300 MHz, acetone-d6) .delta. ppm 9.18 (s, 1H);
8.83 (s, 1H); 8.38 (s, 1H); 8.15 (s, 1H); 4.52 (s, 3H); 3.88 (s,
3H); 3.57 (m, 2H); 1.21 (t, 3H).
A36: .sup.1H NMR (600 MHz, CDCl.sub.3) .delta. ppm 1.29 (t, J=7.4
Hz, 3H) 3.53 (br s, 2H) 3.77 (s, 3H) 4.53 (s, 3H) 8.13 (s, 1H) 8.28
(s, 1H) 8.54 (s, 1H) 8.99 (s, 1H).
A37: .sup.1H NMR (600 MHz, CDCl.sub.3) .delta. ppm 1.27 (t, J=7.3
Hz, 3H) 3.46 (br s, 2H) 3.78 (s, 3H) 4.69 (s, 3H) 8.09 (s, 1H) 8.12
(s, 1H) 8.87 (s, 1H) 8.98 (s, 1H)
Example P17: Preparation of
5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]-3H-1,3-benzothiazole-2-thione A38
##STR00171##
2-bromo-5-ethylsulfonyl-4-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyri-
din-2-yl]aniline (C3, see example P15, 139 mg) was heated with
potassium xantoghenate (commercially available, 105.8 mg) in dried
DMF at 120.degree. C. for 1 h under argon. The solution was treated
with saturated solution of ammonium chloride and extracted with
ethyl acetate. The organic phase and aqueous phase were separated
and the organic phase was dried and concentrated under vacuum. The
residue was subjected to column chromatography over silica gel (25
g), eluting with ethyl acetate. The selected fractions were
evaporated to yield
5-ethylsulfonyl-6-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]-3H-1,3-benzothiazole-2-thione A38 (95% purity, 60 mg). LC-MS
(Method A) RT 0.91 (459, MH.sup.+). .sup.1H NMR (400 MHz, DMSO-d6)
.delta. ppm 9.25 (s, 1H), 8.26 (s, 1H), 8.16 (s, 1H), 7.88 (s, 1H),
3.74 (s, 3H), 3.54 (q, 2H), 1.12 (t, 3H).
Example P18: Preparation of
5-cyclopropyl-3-ethylsulfonyl-2-[3-methyl-6-(trifluoromethyl)imidazo[4,5--
c]pyridin-2-yl]quinoline A43
##STR00172##
To a solution of
5-bromo-3-ethylsulfonyl-2-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyri-
din-2-yl]quinolone A42 (See table 8, 0.1 mmol) in toluene (2 mL)
was added cyclopropylboronic acid (15 mg, 0.17 mmol) and
K.sub.3PO.sub.4 (75 mg, 0.35 mmol) and tricyclohexylphosphine (4
mg, 0.01 mmol). The mixture was degassed for 10 min and
Pd(OAc).sub.2 (2 mg, 0.007 mmol) was added. The mixture was heated
at 100.degree. C. for 2 h. The mixture was filtered through a plug
of Celite and concentrated under vacuum. The residue was purified
by column chromatography (CombiFlash Rf150; 10 g SiO.sub.2;
iHEX:EA=4:1) to give the desired product (26 mg; 56.5%). .sup.1H
NMR: See table 8.
Example P19: Preparation of
3-ethylsulfonyl-2-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]quinoline-6-carbonitrile A50
##STR00173##
A solution of
6-chloro-3-ethylsulfonyl-2-[3-methyl-6-(trifluoromethyl)imidazo[4,5-b]pyr-
idin-2-yl]quinolone A49 (See table 8, 86 mg, 0.19 mmol),
Pd.sub.2dba.sub.3 (27 mg, 0.03 mmol), S-Phos (32 mg, 0.08 mmol) and
Zn(CN).sub.2 (45 mg, 0.38 mmol) in 4 mL of a mixture of DMF:water
(99:1) was heated to 170.degree. C. for 30 min in the microwave
reactor. The solution was diluted with water and extracted with
ethylacetate (2.times). The combined organic layers were
combinated, dried over MgSO4, filtered and concentrated to give an
oil. The oil was purified on silica gel, FCC (CombiFlash Rf150; 10
g SiO2; iHEX:EA=3:1.fwdarw.2:1) to afford the title compound (42
mg; 49.6% yield). .sup.1H NMR: See table 8.
Example P20: Preparation of
3-ethylsulfonyl-2-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c]pyridin-2-yl-
]-6-(1,1,2,2,2-pentafluoroethyl)quinoline A52
##STR00174##
A 5 mL MW vial under argon was charged with A45 (see table 8, 24
mg, 0.48 mmol), NMP (3972 mg, 3.845 mL, 39.7 mmol, 82.5) and
pentafluoroethylator (369.2 mg, 0.96 mmol). The mixture was stirred
at 90.degree. C. for 3 hour and 1 eq. of pentafluoroethylator was
added and MW Vial was put 1 hour more at 90.degree. C. The reaction
mixture was diluted with water (30 ml) and extracted twice with
ethyl acetate (3.times.30 mL). The combined organic phases were
dried over sodium sulfate and concentrated under reduced pressure.
The residue was subjected to column chromatography over silica gel,
eluting with ethyl acetate/cyclohexane. The selected fractions were
evaporated to yield the title compound (118 mg). .sup.1H NMR: See
table 8.
Example P20: Preparation of
2-[6-ethylsulfanyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-b]pyridine A53,
2-[6-ethylsulfanyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethylsulfanyl)imidazo[4,5-b]pyridine A54,
2-[6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-b]pyridine A55,
2-[6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethylsulfanyl)imidazo[4,5-b]pyridine A56 and
2-[6-ethylsulfonyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethylsulfinyl)imidazo[4,5-b]pyridine A57
##STR00175##
A53 and A54 were synthesized by the same protocol using
N2-methyl-5-(trifluoromethyl)pyridine-2,3-diamine (cas:
1643139-91-6) and
N2-methyl-5-(trifluoromethylsulfanyl)pyridine-2,3-diamine (cas:
1383840-73-0) with the intermediate 8.
##STR00176##
A55 and A56 were synthesized by the same protocol for A3 using
2-[6-ethylsulfanyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethyl)imidazo[4,5-b]pyridine A53 and
2-[6-ethylsulfanyl-1-methyl-2-(trifluoromethyl)benzimidazol-5-yl]-3-methy-
l-6-(trifluoromethylsulfanyl)imidazo[4,5-b]pyridine A54.
##STR00177##
A57 was isolated as a byproduct with the compound A56.
TABLE-US-00018 NMR LC/MS A53 .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. ppm 1.23 (t, 3 LC-MS (Method A): RT 1.12 (461, MH.sup.+).
H), 2.88 (q, 2 H), 3.74 (s, 3 H), 4.03 (s, 3 H), 7.59 (s, 1 H),
7.97 (s, 1 H), 8.35 (d, 1 H), 8.74 (d, 1 H). A54 .sup.1H NMR (400
MHz, CDCl.sub.3) .delta. ppm 1.24 (t, 4 LC-MS (Method A): RT 1.18
(492, MH.sup.+). H), 2.89 (q, 2 H), 3.72 (s, 3 H), 4.03 (s, 3 H)
7.58 (s, 1 H) 7.96 (s, 1 H) 8.42 (d, 1 H) 8.68 (d, 1 H). A55
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. ppm 1.28 (t, 3 LC-MS
(Method A): RT 1.03 (492, MH.sup.+). H), 3.56 (q, 2 H), 3.70 (s, 3
H), 4.16 (s, 3 H), 8.04 (s, 1 H), 8.30 (d, 1 H), 8.43 (s, 1 H),
8.76 (d, 1 H). A56 .sup.1H NMR (400 MHz, CDCl.sub.3).delta. ppm
1.28 (m, 3 LC-MS (Method A): RT 1.09 (525, MH.sup.+). H), 3.56 (q,
2 H), 3.69 (s, 3 H), 4.16 (s, 3 H), 8.04 (s, 1 H), 8.37 (d, 1 H),
8.43 (s, 1 H), 8.70 (d, 1 H). A57 .sup.1H NMR (400 MHz, CDCl.sub.3)
.delta. ppm 1.28 (m, 3 LC-MS (Method A): RT 0.96 (540, MH.sup.+).
H), 3.56 (q, 2 H,) 3.73 (s, 3 H), 4.16 (s, 3 H), 8.06 (s, 1 H),
8.44 (s, 1 H), 8.57 (s, 1 H), 8.77 (d, 1 H).
Example P20: Preparation of
6-ethylsulfanyl-2,2-dimethyl-5-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c-
]pyridin-2-yl]-3H-furo[3,2-b]pyridine A58 and
6-ethylsulfonyl-2,2-dimethyl-5-[3-methyl-6-(trifluoromethyl)imidazo[4,5-c-
]pyridin-2-yl]-3H-furo[3,2-b]pyridine A59
##STR00178##
##STR00179##
Step A: Preparation of Compound 2
A solution of NaNO.sub.2 (7.21 g, 126 mmol) in 100 ml of water was
added to a mixture of compound 1 (16.3 g, 100 mmol) in 200 ml of
HBF.sub.4 (40%) when the temperature was dropped to
-5.about.0.degree. C. After stirring at 0.degree. C. for 1 h the
reaction mixture was filtered. The filter residue was washed with
water two times and with ether at 0.degree. C. two times. The crude
product (24.6 g, y: 93%) was used for the next step.
Step A: Preparation of Compound 3
The compound 2 (24.6 g) was added slowly to 250 ml of acetic acid
when the temperature was heated to 70.degree. C..about.90.degree.
C. Then the mixture solution was stirred for 2 h at
80.about.90.degree. C.
The reaction mixture was concentrated and poured into water,
extracted with ethyl acetate three times. The combined organic
layers were dried over sodium sulfate, filtered and concentrated
under vacuum.
The crude product was purified by column chromatography on silica
gel to provide product 3 (7.7 g, y: 37%). .sup.1H NMR (400 MHz,
DMSO-d6) .delta. (ppm): 2.32 (s, 3H), 8.17 (d, 1H), 8.33 (d,
1H).
Step C: Preparation of Compound 4
A solution of KOH (728 mg, 13 mmol) in 7 ml of water was added to a
solution of compound 3 (1 g, 4.8 mmol) in 10 ml of THF at 0.degree.
C. After addition, the mixture was stirred at ambient temperature
for 2 h. Then the mixture added dilute hydrochloric acid
to adjust the pH value to weak alkaline and filtered. The filter
residue was purified by recrystallization to give compound 4 (517
mg, y: 65%). .sup.1H NMR (400 MHz, DMSO-d6) .delta. (ppm): 7.47 (d,
1H), 7.93 (d, 1H), 10.72 (s, 1H).
Step D: Preparation of Compound 5
A mixture of compound 4 (8.15 g, 0.05 mmol), PMBCl (11.78 g, 0.075
mmol) and K.sub.2CO.sub.3 (13.8 g, 0.1 mmol) in 130 ml of
CH.sub.3CN was refluxed under nitrogen for 6 h. Then, the reaction
mixture was filtered. The filtrate was concentrated and purified by
recrystallization to give compound 5 (8.8 g, y: 67%). .sup.1H NMR
(400 Mz, CDCl.sub.3) .delta. (ppm): 3.81 (s, 3H), 5.00 (s, 2H),
6.91 (d, 2H), 7.30 (d, 2H), 7.37 (s, 1H), 8.03 (s, 1H).
Step E: Preparation of Compound 6
A mixture of compound 5 (10 g, 35 mmol), Pd(OAc).sub.2 (158 mg, 0.7
mmol), dppf (975 mg, 1.8 mmol) and Et.sub.3N (10.2 g, 70 mmol) in
120 ml of ethanol was placed in a high pressure vessel and added CO
gas. The press was controlled at 20 bar. Then the reaction mixture
was stirred at 100-120.degree. C. for 6 h. After reaction, the
mixture was filtered. The filtrate was concentrated and purified by
column chromatography on silica gel to provide product 6 (6 g, y:
53%). .sup.1H NMR (400 MHz, DMSO-d6) .delta. (ppm): 1.31 (t, 3H),
3.76 (s, 3H), 4.33 (q, 2H), 5.20 (s, 2H), 6.95 (d, 2H), 7.41 (d,
2H), 7.78 (d, 1H), 8.36 (d, 1H).
Step F: Preparation of Compound 7
Compound 6 (11 g, 34.2 mmol) was dissolved in DMF (60 ml) and EtSNa
(5.75 g, 68.4 mmol) was added when the temperature was dropped to
0.degree. C. After the mixture was stirred at r.t for 0.5 h, it was
poured into the water and extracted with ethyl acetate three times.
The combined organic layers were dried over sodium sulfate,
filtered and concentrated under vacuum. The crude product was
purified by recrystallization to give compound 7 (4.77 g, y:
61%).sup.1H NMR (400 Mz, CDCl.sub.3) .delta. (ppm): 1.33 (t, 3H),
1.40 (t, 3H), 2.83 (q, 2H), 3.79 (s, 3H), 4.42 (q, 2H), 5.09 (s,
3H), 6.90 (d, 2H), 7.11 (s, 1H), 7.32 (d, 2H), 8.16 (s, 1H).
Step G: Preparation of Compound 8
A mixture of compound 7 (10.64 g, 30.66 mmol) and NaOH (3.67 g, 92
mmol) in 90 ml of water and 90 ml of THF was stirred at ambient
temperature for 16 h. Then, the reaction mixture was poured into
diluted hydrochloric acid and extracted with ethyl acetate three
times. The combined organic layers were dried over sodium sulfate,
filtered and concentrated under vacuum. The crude product was
purified by recrystallization to provide product 8 (9 g, y: 92%).
.sup.1H NMR (400 MHz, CDCl.sub.3) .delta. (ppm): 1.36 (t, 3H), 2.85
(q, 2H), 3.80 (s, 3H), 5.12 (s, 2H), 6.92 (d, 2H), 7.14 (s, 1H),
7.33 (d, 2H), 7.99 (s, 1H), 10.98 (s, 1H).
Step H: Preparation of Compound 9
A mixture of N3-methyl-6-(trifluoromethyl)pyridine-3,4-diamine
(Prepared in WO 2015000715, 2.5 g, 15.6 mmol), compound 8 (5 g,
15.6 mmol) and EDC.HCl (3.3 g, 17.2 mmol) in 50 ml of pyridine was
refluxed for 16 h. Then, the mixture was concentrated, diluted with
ethyl acetate and washed with NaHCO.sub.3 saturated solution three
times. The combined organic layers were dried over sodium sulfate,
filtered and concentrated under vacuum. The crude product in 100 ml
of acetic acid was refluxed overnight. Then the mixture was
concentrated and added Na.sub.2CO.sub.3 saturated solution to
adjust the PH value to weak alkaline.
The mixture solution was diluted with ethyl acetate three times,
dried over sodium sulfate, filtered and concentrated under vacuum.
The crude product was purified by column chromatography on silica
gel to provide product 9 (1.93 g, y: 35%). .sup.1H NMR (400 MHz,
DMSO-d6) .delta. (ppm): 1.18 (t, 3H), 2.91 (q, 2H), 3.93 (s, 3H),
7.30 (s, 1H), 8.08 (s, 1H), 8.19 (s, 1H), 9.15 (s, 1H), 10.70 (s,
1H). .sup.19F-NMR (300 Mz, CDCl.sub.3) .delta.: -64.35 (s, 3F).
##STR00180##
Step I: Preparation of Compound 10
Compound 9 (1 mmol, 354 mg), Methylallyl chloride (109 mg, 1.2
mmol), K.sub.2CO.sub.3 (0.8 mmol, 110 mg), and KI(0.012 mmol, 2 mg)
in 4 ml of Acetone and 1 ml of DMF were refluxed for 8 h. Then the
mixture was poured into water, and extracted with ethyl acetate
three times. The combined organic layers were dried over sodium
sulfate, filtered and concentrated under vacuum. The crude product
was purified by column chromatography on silica gel to give product
10 (240 mg, y: 58%). .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
(ppm): 1.33 (t, 3H), 1.85 (s, 3H), 2.91 (q, 2H), 4.02 (s, 3H), 4.59
(s, 2H), 5.10 (d, 2H), 5.27 (s, 1H), 7.25 (d, 1H), 8.15 (s, 1H),
8.19 (d, 19), 8.90 (s, 1H). .sup.19F-NMR (300 Mz, CDCl.sub.3)
.delta.: -66.33 (s, 3F).
Step J: Preparation of Compound A58
Compound 10 (3.1 mmol, 0.83 g) in 10 ml of NMP was stirred under
nitrogen at 185.degree. C. for 24 h. Then the mixture was poured
into water, and extracted with ethyl acetate three times. The
combined organic layers were dried over sodium sulfate, filtered
and concentrated under vacuum. The crude product in 10 ml of
HCO.sub.2H was refluxed for 1 h. Then, the mixture solution was
poured into water and extracted with ethyl acetate three times. The
combined organic layers were dried over sodium sulfate, filtered
and concentrated under vacuum. The crude product was purified by
column chromatography on silica gel to provide product A58 (100 mg,
y: 12%) and the by-product 14 (41 mg, y: 5%).
Compound A58: .sup.1H NMR (400 MHz, CDCl.sub.3) .delta. (ppm): 1.27
(t, 3H), 1.57 (s, 6H), 2.85 (q, 2H), 3.15 (s, 2H), 3.94 (s, 3H),
7.08 (s, 1H), 8.14 (s, 1H), 8.90 (s, 1H). .sup.19F-NMR (300 Mz,
CDCl.sub.3) .delta.: -70.7 (s, 3F). The compound 13 was isolated
with 91% of purity and used, for the next step, without extra
purification.
Compound 14 (by-product): .sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
(ppm): 1.10 (t, 3H), 1.57 (s, 6H), 2.68 (q, 2H), 3.19 (s, 2H), 3.88
(s, 3H), 8.12 (s, 1H), 8.13 (s, 1H), 8.90 (s, 1H). .sup.19F-NMR
(300 Mz, CDCl.sub.3) .delta.: -70.7 (s, 3F).
Step J: Preparation of Compound A59
Compound A58 (0.24 mmol, 100 mg) and m-CPBA (0.87 mmol, 150 mg) in
10 ml of DCM was stirred at ambient temperature for 4 h. Then the
mixture was poured into a saturated solution of NaHCO.sub.3 and
Na.sub.2SO.sub.3 in water, and extracted with ethyl acetate three
times. The combined organic layers were dried over sodium sulfate,
filtered and concentrated under vacuum. The crude product was
purified by column chromatography on silica gel to give tittle
product (70 mg, y: 66%).sup.1H NMR (400 MHz, CDCl.sub.3) .delta.
(ppm): 1.31 (t, 3H), 1.62 (s, 6H), 3.26 (s, 2H), 3.60 (q, 2H), 3.83
(s, 3H), 7.66 (s, 1H), 8.08 (s, 1H), 8.94 (s, 1H); .sup.19F-NMR
(300 Mz, CDCl.sub.3) .delta.: -71.61 (s, 3F).
TABLE-US-00019 TABLE 5 This table discloses compounds of formula
I-1a: ##STR00181## Comp. No. X R.sub.1 R.sub.2 A R.sub.6 A1 S
--CH.sub.2CH.sub.3 CF.sub.3 CH CH.sub.3 (1.001) A2 SO
--CH.sub.2CH.sub.3 CF.sub.3 CH CH.sub.3 (1.002) A3 SO2
--CH.sub.2CH.sub.3 CF.sub.3 CH CH.sub.3 (1.003) A4 S
--CH.sub.2CH.sub.3 CF.sub.3 N CH.sub.3 (1.004) A5 SO
--CH.sub.2CH.sub.3 CF.sub.3 N CH.sub.3 (1.005) A6 SO2
--CH.sub.2CH.sub.3 CF.sub.3 N CH.sub.3 (1.006)
TABLE-US-00020 TABLE 6 This table discloses compounds of formula
I-1a1: ##STR00182## Comp. No. X R.sub.1 R.sub.2 A L.sub.1 L.sub.2
L.sub.3 L.sub.4 A7 SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH NH
C--CF.sub.3 N -- (2.094) A8 SO2 --CH.sub.2CH.sub.3 CF.sub.3 CH N
C--CF.sub.3 N--CH.sub.3 -- (2.126) A9 SO.sub.2 --CH.sub.2CH.sub.3
CF.sub.3 CH N-CH.sub.3 C--CF.sub.3 N - (2.114) Al 0 SO.sub.2
--CH.sub.2CH.sub.3 CF.sub.3 CH NH C--H N -- (2.102) All SO.sub.2
--CH.sub.2CH.sub.3 CF.sub.3 CH N C--H N--CH.sub.3 -- (2.118) Al2
SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH N-CH.sub.3 C--H N --
(2.106) A13 SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH NH C--CH.sub.3
N -- (2.098) A14 SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH N
C--CH.sub.3 N--CH.sub.3 -- (2.122) A15 SO.sub.2 --CH.sub.2CH.sub.3
CF.sub.3 CH N-CH3 C--CH.sub.3 N -- (2.110) A16 SO.sub.2
--CH.sub.2CH.sub.3 CF.sub.3 CH NH C--Ph N -- A17 SO.sub.2
--CH.sub.2CH.sub.3 CF.sub.3 CH NH N N -- (2.046) A18 SO.sub.2
--CH.sub.2CH.sub.3 CF.sub.3 CH N S N -- (2.042) A19 SO.sub.2
--CH.sub.2CH.sub.3 CF.sub.3 CH S C--CH.sub.3 N -- (2.086) A20
SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH N CH CH N A25 S
--CH.sub.2CH.sub.3 CF.sub.3 CH CH N CH CH (2.021) A26 SO.sub.2
--CH.sub.2CH.sub.3 CF.sub.3 CH CH N CH CH (2.022) A27 SO.sub.2
--CH.sub.2CH.sub.3 CF.sub.3 CH CH N.sup.+--O.sup.- CH CH A28
SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH N CH C--CF.sub.3 N A29
SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH N C--CF.sub.3 CH N A30
SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH N CH S -- (2.070) A31
SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH N C--CF.sub.3 S -- (2.078)
A32 SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 N N C--CF.sub.3
N--CH.sub.3 -- (2.128) A33 SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 N
N-CH.sub.3 C--CF.sub.3 N -- (2.116) A34 SO.sub.2 --CH.sub.2CH.sub.3
CF.sub.3 N NH C--CF.sub.3 N -- (2.096) A35 SO.sub.2
--CH.sub.2CH.sub.3 CF.sub.3 CH N N N--CH.sub.3 -- (2.054) A36
SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH N-CH.sub.3 N N -- (2.058)
A37 SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH N N--CH.sub.3 N --
(2.050) A38 SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH N C--SH S --
A39 S --CH.sub.2CH.sub.3 CF.sub.3 CH N-CH.sub.3 C--CF.sub.3 N --
(2.113) A58 S --CH.sub.2CH.sub.3 CF.sub.3 N 0 C(CH3)2 CH.sub.2 --
A59 SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 N 0 C(CH3)2 CH.sub.2
--
TABLE-US-00021 TABLE 7 This table discloses compounds of formula
I-1a3: ##STR00183## Comp. No. X R.sub.1 R.sub.2 A R.sub.6 A21 S
--CH.sub.2CH.sub.3 CF.sub.3 N CH.sub.3 (2.004) A22 SO.sub.2
--CH.sub.2CH.sub.3 CF.sub.3 N CH.sub.3 (2.006) A23 S
--CH.sub.2CH.sub.3 CF.sub.3 CH CH.sub.3 (2.001) A24 SO.sub.2
--CH.sub.2CH.sub.3 CF.sub.3 CH CH.sub.3 (2.003)
TABLE-US-00022 TABLE 8 This table discloses compounds of formula
I-1a4: ##STR00184## Comp. No. X G.sub.1 G.sub.2 R.sub.2 A L.sub.1
L.sub.2 Analytic data/information A39 S N CH CF.sub.3 N CCl CH
Prepared from intermediate 4, using a similar protocol as described
in Example P1. LC- MS (Method 1) RT 1.21, 423 (MH). .sup.1H NMR
(300 MHz, DMSO) ppm 9.309 (s, 1 H); 8.505 (s, 1 H); 8.341 (s, 1 H);
8.124 (d, 1 H); 7.955. (d, 1 H); 7.813 (dd, 1 H); 4.061 (s, 3 H);
3.183 (q, 2 H); 1.306 (t, 3 H). A40 SO.sub.2 N CH CF.sub.3 N CCl CH
Prepared from A39, using a similar protocol as described in Example
P3. LC-MS (Method 1) RT 1.10 455 (MH.sup.+). .sup.1H NMR (300 MHz,
DMSO) ppm 9.328 (s, 1 H); 9.248 (d, 1 H); 8.349 (d, 1 H); 8.306 (m,
1 H); 8.193- 8.117 (m, 2 H); 3.941 (s, 3 H); 3.915 (q, 2 H); 1.249
(t, 3 H). A41 S N CH CF.sub.3 N CBr CH Prepared from intermediate
5, using a similar protocol as described in Example P1. LC- MS
(Method 1) RT 1.21, 469(MH.sup.+). .sup.1H NMR (300 MHz, DMSO) ppm
9.309 (s, 1 H); 8.452 (s, 1 H); 8.342 (d, 1 H); 8.174-8.112 (m, 2
H); 7.750 (dd, 1 H); 4.066 (s, 3 H); 3.173 (q, 2 H); 1.320 (t, 3
H). A42 SO.sub.2 N CH CF.sub.3 N CBr CH Prepared from A41, using a
similar protocol as described in Example P3. LC-MS (Method 1) RT
1.09 501 (MH.sup.+). .sup.1H NMR (300 MHz, DMSO) ppm 9.327 (s, 1
H); 9.215 (s, 1 H); 8.331 (m, 3 H); 8.075 (dd, 1 H); 3.939 (s, 3
H); 3.917 (q, 2 H); 1.248 (t, 3 H). A43 SO.sub.2 N CH CF.sub.3 N C-
CH Example P18: .sup.1H NMR (300 Cyclopropyl MHz, DMSO) ppm 9.570
(d, 1 H); 9.004 (s, 1 H); 8.137 (s, 1 H); 8.088 (dd, 1 H); 7.912
(dd; 1 H); 7.599 (d; 1 H); 3.943 (s, 3 H); 3.848 (q, 2 H); 2.497
(m; 1 H); 1.402 (t, 3 H); 1.241 (m; 2 H); 0.895 (m; 2 H). A44 S N
CH CF.sub.3 N CH CBr Prepared from intermediate 7, using a similar
protocol as described in Example P1. LC- MS (Method 1) RT 1.19, 469
(MH.sup.+). .sup.1H NMR (300 MHz, DMSO) ppm 9.294 (s, 1 H); 8.541
(s, 1 H); 8.383 (d, 1 H); 8.321 (d, 1 H); 8.041 (d, 1 H); 7.922
(dd; 1 H); 4.040 (s, 3 H); 3.112 (q, 2 H); 1.282 (t, 3 H). A45
SO.sub.2 N CH CF.sub.3 N CH CBr Prepared from A44, using a similar
protocol as described in Example P3. LC-MS (Method 1) RT 1.11,
501(MH.sup.+). .sup.1H NMR (300 MHz, DMSO) ppm 9.320 (s, 2 H);
8.825 (d, 1 H); 8.331 (d, 1 H); 8.30-8.20 (m, 2 H); 3.925 (s, 3 H);
3.844 (q, 2 H); 1.228(t, 3 H). A46 S N CH CF.sub.3 N CH CCl
Prepared from intermediate 6, using a similar protocol as described
in Example P1. LC- MS (Method 1) RT 1.18, 423 (MH.sup.+). .sup.1H
NMR (300 MHz, DMSO) ppm 9.295 (s, 1 H); 8.546 (s, 1 H); 8.324 (s, 1
H); 8.219 (d, 1 H); 8.118 (d, 1 H); 7.815 (dd, 1 H); 4.043 (s, 3
H); 3.114 (q, 2 H); 1.284 (t, 3 H). A47 SO.sub.2 N CH CF.sub.3 N CH
CCl Prepared from A46, using a similar protocol as described in
Example P3. LC-MS (Method 1) RT 1.10, 455 (MH.sup.+). .sup.1H NMR
(300 MHz, DMSO) ppm 9.328 (s, 1 H); 9.324 (d, 1 H); 8.670 (d, 1 H);
8.331 (d, 1 H); 8.300 (d, 1 H); 8.158 (dd, 1 H); 3.927 (s, 3 H);
3.847 (q, 2 H); 1.230 (t, 3 H). A48 S CH N CF.sub.3 N CH CCl
Prepared from intermediate 6, using a similar protocol as described
in Example P1. LC- MS (Method 1) RT 1.28, 423 (MH.sup.+). .sup.1H
NMR (300 MHz, DMSO) ppm 8.900 (dd, 1 H); 8.707 (dd, 1 H); 8.531 (s,
1 H); 8.212 (d, 1 H); 8.120 (d, 1 H); 8.707 (d, 1 H); 3.998 (s, 3
H; ) 3.120 (q, 2 H); 1.297 (t, 3 H). A49 SO.sub.2 CH N CF.sub.3 N
CH CCl Prepared from A48, using a similar protocol as described in
Example P3. LC-MS (Method 1) RT 1.17, 455(MH.sup.+). .sup.1H NMR
(300 MHz, DMSO) ppm9.331 (s, 1 H); 8.925 (dd, 1 H); 8.717 (dd, 1
H); 8.668 (d, 1 H); 8.309 (d, 1 H); 8.156 (dd, 1 H); 3.888 (q, 2
H); 3.834 (s, 3 H); 1.244 (t, 3 H). A50 SO.sub.2 N CH CF.sub.3 N CH
CCN .sup.1H NMR (300 MHz, DMSO) ppm 9.452 (s, 1 H); 9.332 (s, 1 H);
9.151 (s, 1 H); 8.433 (s, 1 H); 8.429 (s, 1 H); 8.48 (d, 1 H);
3.951 (s, 3 H; ) 3.880 (q, 2 H); 1.245(t, 3 H). A51 SO.sub.2 N CH
CF.sub.3 N CH C- Prepared as described for A43: cyclopropyl .sup.1H
NMR (300 MHz, DMSO) ppm 9.306 (s, 1 H); 9.152 (s, 1 H); 8.315 (d, 1
H); 8.171 (s, 1 H); 8.154 (d, 1 H); 7.882 (dd, 1 H); 3.904 (s, 3 H;
) 3.818 (q, 2 H); 2.254 (m; 1 H(; 1.242-0.80 (m; 7 H). A52 SO.sub.2
N CH CF.sub.3 N CH CC.sub.2F.sub.5 .sup.1H NMR (400 MHz,
CDCl.sub.3) .quadrature. ppm 1.39-1.42 (m, 3 H) 3.90 (q, J = 7.34
Hz, 2 H) 3.95-4.01 (m, 3 H) 8.11-8.23 (m, 2 H) 8.37-8.50 (m, 2 H)
9.04 (s, 1 H) 9.21 (s, 1 H).
TABLE-US-00023 TABLE 9 This table discloses compounds of formula
I-1a5: ##STR00185## Comp. No. X R.sub.1 R.sub.2 A L.sub.1 L.sub.2
L.sub.3 L.sub.4 A53 S --CH.sub.2CH.sub.3 CF.sub.3 CH N--CH.sub.3
C--CF.sub.3 N -- A54 S --CH.sub.2CH.sub.3 CF.sub.3S CH N--CH.sub.3
C--CF.sub.3 N -- A55 SO.sub.2 --CH.sub.2CH.sub.3 CF.sub.3 CH
N--CH.sub.3 C--CF.sub.3 N -- A56 SO.sub.2 --CH.sub.2CH.sub.3
CF.sub.3S CH N--CH.sub.3 C--CF.sub.3 N -- A57 SO.sub.2
--CH.sub.2CH.sub.3 CF.sub.3S(O) CH N--CH.sub.3 C--CF.sub.3 N -
--
TABLE-US-00024 TABLE 10 This table discloses compounds of formula
I-1a6: ##STR00186## Comp. No. X R.sub.1 R.sub.2 A L.sub.1 L.sub.2
L.sub.3 L.sub.4 Analytic data/information A60 S --CH.sub.2CH.sub.3
CF.sub.3 CH N--CH.sub.3 C--CF.sub.3 N -- Prepared as described for
A39 (example P4b) with N1-methyl-4- (trifluoromethyl)benzene-1,2-
diamine (commercially available) and intermediate 8:.sup.1H NMR
(400 MHz,CDCl.sub.3) .delta. ppm 8.14 (s, 1H), 7.96 (S, 1H), 7.62
(dd, 1 H), 7.56 (s, 1 H), 7.51 (d, 1 H), 4.02 (s, 3 H), 3.65 (s, 3
H), 2.85 (q, 2 H), 1.22 (t, 3 H). A61 SO2 --CH.sub.2CH.sub.3 CF3 CH
N--CH.sub.3 C--CF.sub.3 N -- Prepared from A60 as described for A9
(example P3, Step C): .sup.1H NMR (400 MHz,CDCl.sub.3) .delta. ppm
8.42 (s, 1 H), 8.08 (s, 1 H), 8.03 (s, 1 H), 7.64 (dd, 1 H), 7.53
(d, 1 H), 4.15 (s, 3 H), 3.61 (s, 3 H), 3.55 (br. s., 2 H), 1.26
(t, 3 H).
The activity of the compositions according to the invention can be
broadened considerably, and adapted to prevailing circumstances, by
adding other insecticidally, acaricidally and/or fungicidally
active ingredients. The mixtures of the compounds of formula I with
other insecticidally, acaricidally and/or fungicidally active
ingredients may also have further surprising advantages which can
also be described, in a wider sense, as synergistic activity. For
example, better tolerance by plants, reduced phytotoxicity, insects
can be controlled in their different development stages or better
behaviour during their production, for example during grinding or
mixing, during their storage or during their use.
Suitable additions to active ingredients here are, for example,
representatives of the following classes of active ingredients:
organophosphorus compounds, nitrophenol derivatives, thioureas,
juvenile hormones, formamidines, benzophenone derivatives, ureas,
pyrrole derivatives, carbamates, pyrethroids, chlorinated
hydrocarbons, acylureas, pyridylmethyleneamino derivatives,
macrolides, neonicotinoids and Bacillus thuringiensis
preparations.
The following mixtures of the compounds of formula I with active
ingredients are preferred (the abbreviation "TX" means "one
compound selected from the group consisting of the compounds
described in Table 1 to 10 of the present invention"):
an adjuvant selected from the group of substances consisting of
petroleum oils (628)+TX,
an acaricide selected from the group of substances consisting of
1,1-bis(4-chlorophenyl)-2-ethoxyethanol (IUPAC name) (910)+TX,
2,4-dichlorophenyl benzenesulfonate (IUPAC/Chemical Abstracts name)
(1059)+TX, 2-fluoro-N-methyl-N-1-naphthylacetamide (IUPAC name)
(1295)+TX, 4-chlorophenyl phenyl sulfone (IUPAC name) (981)+TX,
abamectin (1)+TX, acequinocyl (3)+TX, acetoprole [CCN]+TX,
acrinathrin (9)+TX, aldicarb (16)+TX, aldoxycarb (863)+TX,
alpha-cypermethrin (202)+TX, amidithion (870)+TX, amidoflumet
[CCN]+TX, amidothioate (872)+TX, amiton (875)+TX, amiton hydrogen
oxalate (875)+TX, amitraz (24)+TX, aramite (881)+TX, arsenous oxide
(882)+TX, AVI 382 (compound code)+TX, AZ 60541 (compound code)+TX,
azinphos-ethyl (44)+TX, azinphos-methyl (45)+TX, azobenzene (IUPAC
name) (888)+TX, azocyclotin (46)+TX, azothoate (889)+TX, benomyl
(62)+TX, benoxafos [CCN]+TX, benzoximate (71)+TX, benzyl benzoate
(IUPAC name) [CCN]+TX, bifenazate (74)+TX, bifenthrin (76)+TX,
binapacryl (907)+TX, brofenvalerate+TX, bromocyclen (918)+TX,
bromophos (920)+TX, bromophos-ethyl (921)+TX, bromopropylate
(94)+TX, buprofezin (99)+TX, butocarboxim (103)+TX, butoxycarboxim
(104)+TX, butylpyridaben+TX, calcium polysulfide (IUPAC name)
(111)+TX, camphechlor (941)+TX, carbanolate (943)+TX, carbaryl
(115)+TX, carbofuran (118)+TX, carbophenothion (947)+TX, CGA 50'439
(development code) (125)+TX, chinomethionat (126)+TX, chlorbenside
(959)+TX, chlordimeform (964)+TX, chlordimeform hydrochloride
(964)+TX, chlorfenapyr (130)+TX, chlorfenethol (968)+TX,
chlorfenson (970)+TX, chlorfensulfide (971)+TX, chlorfenvinphos
(131)+TX, chlorobenzilate (975)+TX, chloromebuform (977)+TX,
chloromethiuron (978)+TX, chloropropylate (983)+TX, chlorpyrifos
(145)+TX, chlorpyrifos-methyl (146)+TX, chlorthiophos (994)+TX,
cinerin I (696)+TX, cinerin II (696)+TX, cinerins (696)+TX,
clofentezine (158)+TX, closantel [CCN]+TX, coumaphos (174)+TX,
crotamiton [CCN]+TX, crotoxyphos (1010)+TX, cufraneb (1013)+TX,
cyanthoate (1020)+TX, cyflumetofen (CAS Reg. No.: 400882-07-7)+TX,
cyhalothrin (196)+TX, cyhexatin (199)+TX, cypermethrin (201)+TX,
DCPM (1032)+TX, DDT (219)+TX, demephion (1037)+TX, demephion-O
(1037)+TX, demephion-S (1037)+TX, demeton (1038)+TX, demeton-methyl
(224)+TX, demeton-O (1038)+TX, demeton-O-methyl (224)+TX, demeton-S
(1038)+TX, demeton-S-methyl (224)+TX, demeton-S-methylsulfon
(1039)+TX, diafenthiuron (226)+TX, dialifos (1042)+TX, diazinon
(227)+TX, dichlofluanid (230)+TX, dichlorvos (236)+TX,
dicliphos+TX, dicofol (242)+TX, dicrotophos (243)+TX, dienochlor
(1071)+TX, dimefox (1081)+TX, dimethoate (262)+TX, dinactin
(653)+TX, dinex (1089)+TX, dinex-diclexine (1089)+TX, dinobuton
(269)+TX, dinocap (270)+TX, dinocap-4 [CCN]+TX, dinocap-6 [CCN]+TX,
dinocton (1090)+TX, dinopenton (1092)+TX, dinosulfon (1097)+TX,
dinoterbon (1098)+TX, dioxathion (1102)+TX, diphenyl sulfone (IUPAC
name) (1103)+TX, disulfiram [CCN]+TX, disulfoton (278)+TX, DNOC
(282)+TX, dofenapyn (1113)+TX, doramectin [CCN]+TX, endosulfan
(294)+TX, endothion (1121)+TX, EPN (297)+TX, eprinomectin [CCN]+TX,
ethion (309)+TX, ethoate-methyl (1134)+TX, etoxazole (320)+TX,
etrimfos (1142)+TX, fenazaflor (1147)+TX, fenazaquin (328)+TX,
fenbutatin oxide (330)+TX, fenothiocarb (337)+TX, fenpropathrin
(342)+TX, fenpyrad+TX, fenpyroximate (345)+TX, fenson (1157)+TX,
fentrifanil (1161)+TX, fenvalerate (349)+TX, fipronil (354)+TX,
fluacrypyrim (360)+TX, fluazuron (1166)+TX, flubenzimine (1167)+TX,
flucycloxuron (366)+TX, flucythrinate (367)+TX, fluenetil
(1169)+TX, flufenoxuron (370)+TX, flumethrin (372)+TX, fluorbenside
(1174)+TX, fluvalinate (1184)+TX, FMC 1137 (development code)
(1185)+TX, formetanate (405)+TX, formetanate hydrochloride
(405)+TX, formothion (1192)+TX, formparanate (1193)+TX, gamma-HCH
(430)+TX, glyodin (1205)+TX, halfenprox (424)+TX, heptenophos
(432)+TX, hexadecyl cyclopropanecarboxylate (IUPAC/Chemical
Abstracts name) (1216)+TX, hexythiazox (441)+TX, iodomethane (IUPAC
name) (542)+TX, isocarbophos (473)+TX, isopropyl
O-(methoxyaminothiophosphoryl)salicylate (IUPAC name) (473)+TX,
ivermectin [CCN]+TX, jasmolin I (696)+TX, jasmolin II (696)+TX,
jodfenphos (1248)+TX, lindane (430)+TX, lufenuron (490)+TX,
malathion (492)+TX, malonoben (1254)+TX, mecarbam (502)+TX,
mephosfolan (1261)+TX, mesulfen [CCN]+TX, methacrifos (1266)+TX,
methamidophos (527)+TX, methidathion (529)+TX, methiocarb (530)+TX,
methomyl (531)+TX, methyl bromide (537)+TX, metolcarb (550)+TX,
mevinphos (556)+TX, mexacarbate (1290)+TX, milbemectin (557)+TX,
milbemycin oxime [CCN]+TX, mipafox (1293)+TX, monocrotophos
(561)+TX, morphothion (1300)+TX, moxidectin [CCN]+TX, naled
(567)+TX, NC-184 (compound code)+TX, NC-512 (compound code)+TX,
nifluridide (1309)+TX, nikkomycins [CCN]+TX, nitrilacarb (1313)+TX,
nitrilacarb 1:1 zinc chloride complex (1313)+TX, NNI-0101 (compound
code)+TX, NNI-0250 (compound code)+TX, omethoate (594)+TX, oxamyl
(602)+TX, oxydeprofos (1324)+TX, oxydisulfoton (1325)+TX, pp'-DDT
(219)+TX, parathion (615)+TX, permethrin (626)+TX, petroleum oils
(628)+TX, phenkapton (1330)+TX, phenthoate (631)+TX, phorate
(636)+TX, phosalone (637)+TX, phosfolan (1338)+TX, phosmet
(638)+TX, phosphamidon (639)+TX, phoxim (642)+TX, pirimiphos-methyl
(652)+TX, polychloroterpenes (traditional name) (1347)+TX,
polynactins (653)+TX, proclonol (1350)+TX, profenofos (662)+TX,
promacyl (1354)+TX, propargite (671)+TX, propetamphos (673)+TX,
propoxur (678)+TX, prothidathion (1360)+TX, prothoate (1362)+TX,
pyrethrin I (696)+TX, pyrethrin II (696)+TX, pyrethrins (696)+TX,
pyridaben (699)+TX, pyridaphenthion (701)+TX, pyrimidifen (706)+TX,
pyrimitate (1370)+TX, quinalphos (711)+TX, quintiofos (1381)+TX,
R-1492 (development code) (1382)+TX, RA-17 (development code)
(1383)+TX, rotenone (722)+TX, schradan (1389)+TX, sebufos+TX,
selamectin [CCN]+TX, SI-0009 (compound code)+TX, sophamide
(1402)+TX, spirodiclofen (738)+TX, spiromesifen (739)+TX, SSI-121
(development code) (1404)+TX, sulfiram [CCN]+TX, sulfluramid
(750)+TX, sulfotep (753)+TX, sulfur (754)+TX, SZI-121 (development
code) (757)+TX, tau-fluvalinate (398)+TX, tebufenpyrad (763)+TX,
TEPP (1417)+TX, terbam+TX, tetrachlorvinphos (777)+TX, tetradifon
(786)+TX, tetranactin (653)+TX, tetrasul (1425)+TX, thiafenox+TX,
thiocarboxime (1431)+TX, thiofanox (800)+TX, thiometon (801)+TX,
thioquinox (1436)+TX, thuringiensin [CCN]+TX, triamiphos (1441)+TX,
triarathene (1443)+TX, triazophos (820)+TX, triazuron+TX,
trichlorfon (824)+TX, trifenofos (1455)+TX, trinactin (653)+TX,
vamidothion (847)+TX, vaniliprole [CCN] and YI-5302 (compound
code)+TX,
an algicide selected from the group of substances consisting of
bethoxazin [CCN]+TX, copper dioctanoate (IUPAC name) (170)+TX,
copper sulfate (172)+TX, cybutryne [CCN]+TX, dichlone (1052)+TX,
dichlorophen (232)+TX, endothal (295)+TX, fentin (347)+TX, hydrated
lime [CCN]+TX, nabam (566)+TX, quinoclamine (714)+TX, quinonamid
(1379)+TX, simazine (730)+TX, triphenyltin acetate (IUPAC name)
(347) and triphenyltin hydroxide (IUPAC name) (347)+TX,
an anthelmintic selected from the group of substances consisting of
abamectin (1)+TX, crufomate (1011)+TX, doramectin [CCN]+TX,
emamectin (291)+TX, emamectin benzoate (291)+TX, eprinomectin
[CCN]+TX, ivermectin [CCN]+TX, milbemycin oxime [CCN]+TX,
moxidectin [CCN]+TX, piperazine [CCN]+TX, selamectin [CCN]+TX,
spinosad (737) and thiophanate (1435)+TX,
an avicide selected from the group of substances consisting of
chloralose (127)+TX, endrin (1122)+TX, fenthion (346)+TX,
pyridin-4-amine (IUPAC name) (23) and strychnine (745)+TX, a
bactericide selected from the group of substances consisting of
1-hydroxy-1H-pyridine-2-thione (IUPAC name) (1222)+TX,
4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX,
8-hydroxyquinoline sulfate (446)+TX, bronopol (97)+TX, copper
dioctanoate (IUPAC name) (170)+TX, copper hydroxide (IUPAC name)
(169)+TX, cresol [CCN]+TX, dichlorophen (232)+TX, dipyrithione
(1105)+TX, dodicin (1112)+TX, fenaminosulf (1144)+TX, formaldehyde
(404)+TX, hydrargaphen [CCN]+TX, kasugamycin (483)+TX, kasugamycin
hydrochloride hydrate (483)+TX, nickel bis(dimethyldithiocarbamate)
(IUPAC name) (1308)+TX, nitrapyrin (580)+TX, octhilinone (590)+TX,
oxolinic acid (606)+TX, oxytetracycline (611)+TX, potassium
hydroxyquinoline sulfate (446)+TX, probenazole (658)+TX,
streptomycin (744)+TX, streptomycin sesquisulfate (744)+TX,
tecloftalam (766)+TX, and thiomersal [CCN]+TX,
a biological agent selected from the group of substances consisting
of Adoxophyes orana GV (12)+TX, Agrobacterium radiobacter (13)+TX,
Amblyseius spp. (19)+TX, Anagrapha falcifera NPV (28)+TX, Anagrus
atomus (29)+TX, Aphelinus abdominalis (33)+TX, Aphidius colemani
(34)+TX, Aphidoletes aphidimyza (35)+TX, Autographa californica NPV
(38)+TX, Bacillus firmus (48)+TX, Bacillus sphaericus Neide
(scientific name) (49)+TX, Bacillus thuringiensis Berliner
(scientific name) (51)+TX, Bacillus thuringiensis subsp. aizawai
(scientific name) (51)+TX, Bacillus thuringiensis subsp.
israelensis (scientific name) (51)+TX, Bacillus thuringiensis
subsp. japonensis (scientific name) (51)+TX, Bacillus thuringiensis
subsp. kurstaki (scientific name) (51)+TX, Bacillus thuringiensis
subsp. tenebrionis (scientific name) (51)+TX, Beauveria bassiana
(53)+TX, Beauveria brongniartii (54)+TX, Chrysoperla carnea
(151)+TX, Cryptolaemus montrouzieri (178)+TX, Cydia pomonella GV
(191)+TX, Dacnusa sibirica (212)+TX, Diglyphus isaea (254)+TX,
Encarsia formosa (scientific name) (293)+TX, Eretmocerus eremicus
(300)+TX, Helicoverpa zea NPV (431)+TX, Heterorhabditis
bacteriophora and H. megidis (433)+TX, Hippodamia convergens
(442)+TX, Leptomastix dactylopii (488)+TX, Macrolophus caliginosus
(491)+TX, Mamestra brassicae NPV (494)+TX, Metaphycus helvolus
(522)+TX, Metarhizium anisopliae var. acridum (scientific name)
(523)+TX, Metarhizium anisopliae var. anisopliae (scientific name)
(523)+TX, Neodiprion sertifer NPV and N. lecontei NPV (575)+TX,
Orius spp. (596)+TX, Paecilomyces fumosoroseus (613)+TX,
Phytoseiulus persimilis (644)+TX, Spodoptera exigua multicapsid
nuclear polyhedrosis virus (scientific name) (741)+TX, Steinernema
bibionis (742)+TX, Steinernema carpocapsae (742)+TX, Steinernema
feltiae (742)+TX, Steinernema glaseri (742)+TX, Steinernema
riobrave (742)+TX, Steinernema riobravis (742)+TX, Steinernema
scapterisci (742)+TX, Steinernema spp. (742)+TX, Trichogramma spp.
(826)+TX, Typhlodromus occidentalis (844) and Verticillium lecanii
(848)+TX, a soil sterilant selected from the group of substances
consisting of iodomethane (IUPAC name) (542) and methyl bromide
(537)+TX,
a chemosterilant selected from the group of substances consisting
of apholate [CCN]+TX, bisazir [CCN]+TX, busulfan [CCN]+TX,
diflubenzuron (250)+TX, dimatif [CCN]+TX, hemel [CCN]+TX, hempa
[CCN]+TX, metepa [CCN]+TX, methiotepa [CCN]+TX, methyl apholate
[CCN]+TX, morzid [CCN]+TX, penfluron [CCN]+TX, tepa [CCN]+TX,
thiohempa [CCN]+TX, thiotepa [CCN]+TX, tretamine [CCN] and uredepa
[CCN]+TX,
an insect pheromone selected from the group of substances
consisting of (E)-dec-5-en-1-yl acetate with (E)-dec-5-en-1-ol
(IUPAC name) (222)+TX, (E)-tridec-4-en-1-yl acetate (IUPAC name)
(829)+TX, (E)-6-methylhept-2-en-4-ol (IUPAC name) (541)+TX,
(E,Z)-tetradeca-4,10-dien-1-yl acetate (IUPAC name) (779)+TX,
(Z)-dodec-7-en-1-yl acetate (IUPAC name) (285)+TX,
(Z)-hexadec-11-enal (IUPAC name) (436)+TX, (Z)-hexadec-11-en-1-yl
acetate (IUPAC name) (437)+TX, (Z)-hexadec-13-en-11-yn-1-yl acetate
(IUPAC name) (438)+TX, (Z)-icos-13-en-10-one (IUPAC name) (448)+TX,
(Z)-tetradec-7-en-1-al (IUPAC name) (782)+TX,
(Z)-tetradec-9-en-1-ol (IUPAC name) (783)+TX,
(Z)-tetradec-9-en-1-yl acetate (IUPAC name) (784)+TX,
(7E,9Z)-dodeca-7,9-dien-1-yl acetate (IUPAC name) (283)+TX,
(9Z,11E)-tetradeca-9,11-dien-1-yl acetate (IUPAC name) (780)+TX,
(9Z,12E)-tetradeca-9,12-dien-1-yl acetate (IUPAC name) (781)+TX,
14-methyloctadec-1-ene (IUPAC name) (545)+TX, 4-methylnonan-5-ol
with 4-methylnonan-5-one (IUPAC name) (544)+TX, alpha-multistriatin
[CCN]+TX, brevicomin [CCN]+TX, codlelure [CCN]+TX, codlemone
(167)+TX, cuelure (179)+TX, disparlure (277)+TX, dodec-8-en-1-yl
acetate (IUPAC name) (286)+TX, dodec-9-en-1-yl acetate (IUPAC name)
(287)+TX, dodeca-8+TX, 10-dien-1-yl acetate (IUPAC name) (284)+TX,
dominicalure [CCN]+TX, ethyl 4-methyloctanoate (IUPAC name)
(317)+TX, eugenol [CCN]+TX, frontalin [CCN]+TX, gossyplure
(420)+TX, grandlure (421)+TX, grandlure I (421)+TX, grandlure II
(421)+TX, grandlure III (421)+TX, grandlure IV (421)+TX, hexalure
[CCN]+TX, ipsdienol [CCN]+TX, ipsenol [CCN]+TX, japonilure
(481)+TX, lineatin [CCN]+TX, litlure [CCN]+TX, looplure [CCN]+TX,
medlure [CCN]+TX, megatomoic acid [CCN]+TX, methyl eugenol
(540)+TX, muscalure (563)+TX, octadeca-2,13-dien-1-yl acetate
(IUPAC name) (588)+TX, octadeca-3,13-dien-1-yl acetate (IUPAC name)
(589)+TX, orfralure [CCN]+TX, oryctalure (317)+TX, ostramone
[CCN]+TX, siglure [CCN]+TX, sordidin (736)+TX, sulcatol [CCN]+TX,
tetradec-11-en-1-yl acetate (IUPAC name) (785)+TX, trimedlure
(839)+TX, trimedlure A (839)+TX, trimedlure B.sub.1 (839)+TX,
trimedlure B.sub.2 (839)+TX, trimedlure C (839) and trunc-call
[CCN]+TX,
an insect repellent selected from the group of substances
consisting of 2-(octylthio)ethanol (IUPAC name) (591)+TX,
butopyronoxyl (933)+TX, butoxy(polypropylene glycol) (936)+TX,
dibutyl adipate (IUPAC name) (1046)+TX, dibutyl phthalate
(1047)+TX, dibutyl succinate (IUPAC name) (1048)+TX,
diethyltoluamide [CCN]+TX, dimethyl carbate [CCN]+TX, dimethyl
phthalate [CCN]+TX, ethyl hexanediol (1137)+TX, hexamide [CCN]+TX,
methoquin-butyl (1276)+TX, methylneodecanamide [CCN]+TX, oxamate
[CCN] and picaridin [CCN]+TX,
an insecticide selected from the group of substances consisting of
1-dichloro-1-nitroethane (IUPAC/Chemical Abstracts name) (1058)+TX,
1,1-dichloro-2,2-bis(4-ethylphenyl)ethane (IUPAC name) (1056), +TX,
1,2-dichloropropane (IUPAC/Chemical Abstracts name) (1062)+TX,
1,2-dichloropropane with 1,3-dichloropropene (IUPAC name)
(1063)+TX, 1-bromo-2-chloroethane (IUPAC/Chemical Abstracts name)
(916)+TX, 2,2,2-trichloro-1-(3,4-dichlorophenyl)ethyl acetate
(IUPAC name) (1451)+TX, 2,2-dichlorovinyl 2-ethylsulfinylethyl
methyl phosphate (IUPAC name) (1066)+TX,
2-(1,3-dithiolan-2-yl)phenyl dimethylcarbamate (IUPAC/Chemical
Abstracts name) (1109)+TX, 2-(2-butoxyethoxy)ethyl thiocyanate
(IUPAC/Chemical Abstracts name) (935)+TX,
2-(4,5-dimethyl-1,3-dioxolan-2-yl)phenyl methylcarbamate
(IUPAC/Chemical Abstracts name) (1084)+TX,
2-(4-chloro-3,5-xylyloxy)ethanol (IUPAC name) (986)+TX,
2-chlorovinyl diethyl phosphate (IUPAC name) (984)+TX,
2-imidazolidone (IUPAC name) (1225)+TX, 2-isovalerylindan-1,3-dione
(IUPAC name) (1246)+TX, 2-methyl(prop-2-ynyl)aminophenyl
methylcarbamate (IUPAC name) (1284)+TX, 2-thiocyanatoethyl laurate
(IUPAC name) (1433)+TX, 3-bromo-1-chloroprop-1-ene (IUPAC name)
(917)+TX, 3-methyl-1-phenylpyrazol-5-yl dimethylcarbamate (IUPAC
name) (1283)+TX, 4-methyl(prop-2-ynyl)amino-3,5-xylyl
methylcarbamate (IUPAC name) (1285)+TX,
5,5-dimethyl-3-oxocyclohex-1-enyl dimethylcarbamate (IUPAC name)
(1085)+TX, abamectin (1)+TX, acephate (2)+TX, acetamiprid (4)+TX,
acethion [CCN]+TX, acetoprole [CCN]+TX, acrinathrin (9)+TX,
acrylonitrile (IUPAC name) (861)+TX, alanycarb (15)+TX, aldicarb
(16)+TX, aldoxycarb (863)+TX, aldrin (864)+TX, allethrin (17)+TX,
allosamidin [CCN]+TX, allyxycarb (866)+TX, alpha-cypermethrin
(202)+TX, alpha-ecdysone [CCN]+TX, aluminium phosphide (640)+TX,
amidithion (870)+TX, amidothioate (872)+TX, aminocarb (873)+TX,
amiton (875)+TX, amiton hydrogen oxalate (875)+TX, amitraz (24)+TX,
anabasine (877)+TX, athidathion (883)+TX, AVI 382 (compound
code)+TX, AZ 60541 (compound code)+TX, azadirachtin (41)+TX,
azamethiphos (42)+TX, azinphos-ethyl (44)+TX, azinphos-methyl
(45)+TX, azothoate (889)+TX, Bacillus thuringiensis delta
endotoxins (52)+TX, barium hexafluorosilicate [CCN]+TX, barium
polysulfide (IUPAC/Chemical Abstracts name) (892)+TX, barthrin
[CCN]+TX, Bayer 22/190 (development code) (893)+TX, Bayer 22408
(development code) (894)+TX, bendiocarb (58)+TX, benfuracarb
(60)+TX, bensultap (66)+TX, beta-cyfluthrin (194)+TX,
beta-cypermethrin (203)+TX, bifenthrin (76)+TX, bioallethrin
(78)+TX, bioallethrin S-cyclopentenyl isomer (79)+TX,
bioethanomethrin [CCN]+TX, biopermethrin (908)+TX, bioresmethrin
(80)+TX, bis(2-chloroethyl) ether (IUPAC name) (909)+TX,
bistrifluron (83)+TX, borax (86)+TX, brofenvalerate+TX,
bromfenvinfos (914)+TX, bromocyclen (918)+TX, bromo-DDT [CCN]+TX,
bromophos (920)+TX, bromophos-ethyl (921)+TX, bufencarb (924)+TX,
buprofezin (99)+TX, butacarb (926)+TX, butathiofos (927)+TX,
butocarboxim (103)+TX, butonate (932)+TX, butoxycarboxim (104)+TX,
butylpyridaben+TX, cadusafos (109)+TX, calcium arsenate [CCN]+TX,
calcium cyanide (444)+TX, calcium polysulfide (IUPAC name)
(111)+TX, camphechlor (941)+TX, carbanolate (943)+TX, carbaryl
(115)+TX, carbofuran (118)+TX, carbon disulfide (IUPAC/Chemical
Abstracts name) (945)+TX, carbon tetrachloride (IUPAC name)
(946)+TX, carbophenothion (947)+TX, carbosulfan (119)+TX, cartap
(123)+TX, cartap hydrochloride (123)+TX, cevadine (725)+TX,
chlorbicyclen (960)+TX, chlordane (128)+TX, chlordecone (963)+TX,
chlordimeform (964)+TX, chlordimeform hydrochloride (964)+TX,
chlorethoxyfos (129)+TX, chlorfenapyr (130)+TX, chlorfenvinphos
(131)+TX, chlorfluazuron (132)+TX, chlormephos (136)+TX, chloroform
[CCN]+TX, chloropicrin (141)+TX, chlorphoxim (989)+TX,
chlorprazophos (990)+TX, chlorpyrifos (145)+TX, chlorpyrifos-methyl
(146)+TX, chlorthiophos (994)+TX, chromafenozide (150)+TX, cinerin
I (696)+TX, cinerin II (696)+TX, cinerins (696)+TX,
cis-resmethrin+TX, cismethrin (80)+TX, clocythrin+TX, cloethocarb
(999)+TX, closantel [CCN]+TX, clothianidin (165)+TX, copper
acetoarsenite [CCN]+TX, copper arsenate [CCN]+TX, copper oleate
[CCN]+TX, coumaphos (174)+TX, coumithoate (1006)+TX, crotamiton
[CCN]+TX, crotoxyphos (1010)+TX, crufomate (1011)+TX, cryolite
(177)+TX, CS 708 (development code) (1012)+TX, cyanofenphos
(1019)+TX, cyanophos (184)+TX, cyanthoate (1020)+TX, cyclethrin
[CCN]+TX, cycloprothrin (188)+TX, cyfluthrin (193)+TX, cyhalothrin
(196)+TX, cypermethrin (201)+TX, cyphenothrin (206)+TX, cyromazine
(209)+TX, cythioate [CCN]+TX, d-limonene [CCN]+TX, d-tetramethrin
(788)+TX, DAEP (1031)+TX, dazomet (216)+TX, DDT (219)+TX,
decarbofuran (1034)+TX, deltamethrin (223)+TX, demephion (1037)+TX,
demephion-O (1037)+TX, demephion-S (1037)+TX, demeton (1038)+TX,
demeton-methyl (224)+TX, demeton-O (1038)+TX, demeton-O-methyl
(224)+TX, demeton-S (1038)+TX, demeton-S-methyl (224)+TX,
demeton-S-methylsulphon (1039)+TX, diafenthiuron (226)+TX, dialifos
(1042)+TX, diamidafos (1044)+TX, diazinon (227)+TX, dicapthon
(1050)+TX, dichlofenthion (1051)+TX, dichlorvos (236)+TX,
dicliphos+TX, dicresyl [CCN]+TX, dicrotophos (243)+TX, dicyclanil
(244)+TX, dieldrin (1070)+TX, diethyl 5-methylpyrazol-3-yl
phosphate (IUPAC name) (1076)+TX, diflubenzuron (250)+TX, dilor
[CCN]+TX, dimefluthrin [CCN]+TX, dimefox (1081)+TX, dimetan
(1085)+TX, dimethoate (262)+TX, dimethrin (1083)+TX,
dimethylvinphos (265)+TX, dimetilan (1086)+TX, dinex (1089)+TX,
dinex-diclexine (1089)+TX, dinoprop (1093)+TX, dinosam (1094)+TX,
dinoseb (1095)+TX, dinotefuran (271)+TX, diofenolan (1099)+TX,
dioxabenzofos (1100)+TX, dioxacarb (1101)+TX, dioxathion (1102)+TX,
disulfoton (278)+TX, dithicrofos (1108)+TX, DNOC (282)+TX,
doramectin [CCN]+TX, DSP (1115)+TX, ecdysterone [CCN]+TX, EI 1642
(development code) (1118)+TX, emamectin (291)+TX, emamectin
benzoate (291)+TX, EMPC (1120)+TX, empenthrin (292)+TX, endosulfan
(294)+TX, endothion (1121)+TX, endrin (1122)+TX, EPBP (1123)+TX,
EPN (297)+TX, epofenonane (1124)+TX, eprinomectin [CCN]+TX,
esfenvalerate (302)+TX, etaphos [CCN]+TX, ethiofencarb (308)+TX,
ethion (309)+TX, ethiprole (310)+TX, ethoate-methyl (1134)+TX,
ethoprophos (312)+TX, ethyl formate (IUPAC name) [CCN]+TX,
ethyl-DDD (1056)+TX, ethylene dibromide (316)+TX, ethylene
dichloride (chemical name) (1136)+TX, ethylene oxide [CCN]+TX,
etofenprox (319)+TX, etrimfos (1142)+TX, EXD (1143)+TX, famphur
(323)+TX, fenamiphos (326)+TX, fenazaflor (1147)+TX, fenchlorphos
(1148)+TX, fenethacarb (1149)+TX, fenfluthrin (1150)+TX,
fenitrothion (335)+TX, fenobucarb (336)+TX, fenoxacrim (1153)+TX,
fenoxycarb (340)+TX, fenpirithrin (1155)+TX, fenpropathrin
(342)+TX, fenpyrad+TX, fensulfothion (1158)+TX, fenthion (346)+TX,
fenthion-ethyl [CCN]+TX, fenvalerate (349)+TX, fipronil (354)+TX,
flonicamid (358)+TX, flubendiamide (CAS. Reg. No.: 272451-65-7)+TX,
flucofuron (1168)+TX, flucycloxuron (366)+TX, flucythrinate
(367)+TX, fluenetil (1169)+TX, flufenerim [CCN]+TX, flufenoxuron
(370)+TX, flufenprox (1171)+TX, flumethrin (372)+TX, fluvalinate
(1184)+TX, FMC 1137 (development code) (1185)+TX, fonofos
(1191)+TX, formetanate (405)+TX, formetanate hydrochloride
(405)+TX, formothion (1192)+TX, formparanate (1193)+TX, fosmethilan
(1194)+TX, fospirate (1195)+TX, fosthiazate (408)+TX, fosthietan
(1196)+TX, furathiocarb (412)+TX, furethrin (1200)+TX,
gamma-cyhalothrin (197)+TX, gamma-HCH (430)+TX, guazatine (422)+TX,
guazatine acetates (422)+TX, GY-81 (development code) (423)+TX,
halfenprox (424)+TX, halofenozide (425)+TX, HCH (430)+TX, HEOD
(1070)+TX, heptachlor (1211)+TX, heptenophos (432)+TX, heterophos
[CCN]+TX, hexaflumuron (439)+TX, HHDN (864)+TX, hydramethylnon
(443)+TX, hydrogen cyanide (444)+TX, hydroprene (445)+TX,
hyquincarb (1223)+TX, imidacloprid (458)+TX, imiprothrin (460)+TX,
indoxacarb (465)+TX, iodomethane (IUPAC name) (542)+TX, IPSP
(1229)+TX, isazofos (1231)+TX, isobenzan (1232)+TX, isocarbophos
(473)+TX, isodrin (1235)+TX, isofenphos (1236)+TX, isolane
(1237)+TX, isoprocarb (472)+TX, isopropyl
O-(methoxy-aminothiophosphoryl)salicylate (IUPAC name) (473)+TX,
isoprothiolane (474)+TX, isothioate (1244)+TX, isoxathion (480)+TX,
ivermectin [CCN]+TX, jasmolin I (696)+TX, jasmolin II (696)+TX,
jodfenphos (1248)+TX, juvenile hormone I [CCN]+TX, juvenile hormone
II [CCN]+TX, juvenile hormone Ill [CCN]+TX, kelevan (1249)+TX,
kinoprene (484)+TX, lambda-cyhalothrin (198)+TX, lead arsenate
[CCN]+TX, lepimectin (CCN)+TX, leptophos (1250)+TX, lindane
(430)+TX, lirimfos (1251)+TX, lufenuron (490)+TX, lythidathion
(1253)+TX, m-cumenyl methylcarbamate (IUPAC name) (1014)+TX,
magnesium phosphide (IUPAC name) (640)+TX, malathion (492)+TX,
malonoben (1254)+TX, mazidox (1255)+TX, mecarbam (502)+TX,
mecarphon (1258)+TX, menazon (1260)+TX, mephosfolan (1261)+TX,
mercurous chloride (513)+TX, mesulfenfos (1263)+TX, metaflumizone
(CCN)+TX, metam (519)+TX, metam-potassium (519)+TX, metam-sodium
(519)+TX, methacrifos (1266)+TX, methamidophos (527)+TX,
methanesulfonyl fluoride (IUPAC/Chemical Abstracts name) (1268)+TX,
methidathion (529)+TX, methiocarb (530)+TX, methocrotophos
(1273)+TX, methomyl (531)+TX, methoprene (532)+TX, methoquin-butyl
(1276)+TX, methothrin (533)+TX, methoxychlor (534)+TX,
methoxyfenozide (535)+TX, methyl bromide (537)+TX, methyl
isothiocyanate (543)+TX, methylchloroform [CCN]+TX, methylene
chloride [CCN]+TX, metofluthrin [CCN]+TX, metolcarb (550)+TX,
metoxadiazone (1288)+TX, mevinphos (556)+TX, mexacarbate (1290)+TX,
milbemectin (557)+TX, milbemycin oxime [CCN]+TX, mipafox (1293)+TX,
mirex (1294)+TX, monocrotophos (561)+TX, morphothion (1300)+TX,
moxidectin [CCN]+TX, naftalofos [CCN]+TX, naled (567)+TX,
naphthalene (IUPAC/Chemical Abstracts name) (1303)+TX, NC-170
(development code) (1306)+TX, NC-184 (compound code)+TX, nicotine
(578)+TX, nicotine sulfate (578)+TX, nifluridide (1309)+TX,
nitenpyram (579)+TX, nithiazine (1311)+TX, nitrilacarb (1313)+TX,
nitrilacarb 1:1 zinc chloride complex (1313)+TX, NNI-0101 (compound
code)+TX, NNI-0250 (compound code)+TX, nornicotine (traditional
name) (1319)+TX, novaluron (585)+TX, noviflumuron (586)+TX,
O-5-dichloro-4-iodophenyl O-ethyl ethylphosphonothioate (IUPAC
name) (1057)+TX, O,O-diethyl O-4-methyl-2-oxo-2H-chromen-7-yl
phosphorothioate (IUPAC name) (1074)+TX, O,O-diethyl
O-6-methyl-2-propylpyrimidin-4-yl phosphorothioate (IUPAC name)
(1075)+TX, O,O,O',O'-tetrapropyl dithiopyrophosphate (IUPAC name)
(1424)+TX, oleic acid (IUPAC name) (593)+TX, omethoate (594)+TX,
oxamyl (602)+TX, oxydemeton-methyl (609)+TX, oxydeprofos (1324)+TX,
oxydisulfoton (1325)+TX, pp'-DDT (219)+TX, para-dichlorobenzene
[CCN]+TX, parathion (615)+TX, parathion-methyl (616)+TX, penfluron
[CCN]+TX, pentachlorophenol (623)+TX, pentachlorophenyl laurate
(IUPAC name) (623)+TX, permethrin (626)+TX, petroleum oils
(628)+TX, PH 60-38 (development code) (1328)+TX, phenkapton
(1330)+TX, phenothrin (630)+TX, phenthoate (631)+TX, phorate
(636)+TX, phosalone (637)+TX, phosfolan (1338)+TX, phosmet
(638)+TX, phosnichlor (1339)+TX, phosphamidon (639)+TX, phosphine
(IUPAC name) (640)+TX, phoxim (642)+TX, phoxim-methyl (1340)+TX,
pirimetaphos (1344)+TX, pirimicarb (651)+TX, pirimiphos-ethyl
(1345)+TX, pirimiphos-methyl (652)+TX, polychlorodicyclopentadiene
isomers (IUPAC name) (1346)+TX, polychloroterpenes (traditional
name) (1347)+TX, potassium arsenite [CCN]+TX, potassium thiocyanate
[CCN]+TX, prallethrin (655)+TX, precocene I [CCN]+TX, precocene II
[CCN]+TX, precocene Ill [CCN]+TX, primidophos (1349)+TX, profenofos
(662)+TX, profluthrin [CCN]+TX, promacyl (1354)+TX, promecarb
(1355)+TX, propaphos (1356)+TX, propetamphos (673)+TX, propoxur
(678)+TX, prothidathion (1360)+TX, prothiofos (686)+TX, prothoate
(1362)+TX, protrifenbute [CCN]+TX, pymetrozine (688)+TX, pyraclofos
(689)+TX, pyrazophos (693)+TX, pyresmethrin (1367)+TX, pyrethrin 1
(696)+TX, pyrethrin II (696)+TX, pyrethrins (696)+TX, pyridaben
(699)+TX, pyridalyl (700)+TX, pyridaphenthion (701)+TX, pyrimidifen
(706)+TX, pyrimitate (1370)+TX, pyriproxyfen (708)+TX, quassia
[CCN]+TX, quinalphos (711)+TX, quinalphos-methyl (1376)+TX,
quinothion (1380)+TX, quintiofos (1381)+TX, R-1492 (development
code) (1382)+TX, rafoxanide [CCN]+TX, resmethrin (719)+TX, rotenone
(722)+TX, RU 15525 (development code) (723)+TX, RU 25475
(development code) (1386)+TX, ryania (1387)+TX, ryanodine
(traditional name) (1387)+TX, sabadilla (725)+TX, schradan
(1389)+TX, sebufos+TX, selamectin [CCN]+TX, SI-0009 (compound
code)+TX, SI-0205 (compound code)+TX, SI-0404 (compound code)+TX,
SI-0405 (compound code)+TX, silafluofen (728)+TX, SN 72129
(development code) (1397)+TX, sodium arsenite [CCN]+TX, sodium
cyanide (444)+TX, sodium fluoride (IUPAC/Chemical Abstracts name)
(1399)+TX, sodium hexafluorosilicate (1400)+TX, sodium
pentachlorophenoxide (623)+TX, sodium selenate (IUPAC name)
(1401)+TX, sodium thiocyanate [CCN]+TX, sophamide (1402)+TX,
spinosad (737)+TX, spiromesifen (739)+TX, spirotetrmat (CCN)+TX,
sulcofuron (746)+TX, sulcofuron-sodium (746)+TX, sulfluramid
(750)+TX, sulfotep (753)+TX, sulfuryl fluoride (756)+TX, sulprofos
(1408)+TX, tar oils (758)+TX, tau-fluvalinate (398)+TX, tazimcarb
(1412)+TX, TDE (1414)+TX, tebufenozide (762)+TX, tebufenpyrad
(763)+TX, tebupirimfos (764)+TX, teflubenzuron (768)+TX, tefluthrin
(769)+TX, temephos (770)+TX, TEPP (1417)+TX, terallethrin
(1418)+TX, terbam+TX, terbufos (773)+TX, tetrachloroethane
[CCN]+TX, tetrachlorvinphos (777)+TX, tetramethrin (787)+TX,
theta-cypermethrin (204)+TX, thiacloprid (791)+TX, thiafenox+TX,
thiamethoxam (792)+TX, thicrofos (1428)+TX, thiocarboxime
(1431)+TX, thiocyclam (798)+TX, thiocyclam hydrogen oxalate
(798)+TX, thiodicarb (799)+TX, thiofanox (800)+TX, thiometon
(801)+TX, thionazin (1434)+TX, thiosultap (803)+TX,
thiosultap-sodium (803)+TX, thuringiensin [CCN]+TX, tolfenpyrad
(809)+TX, tralomethrin (812)+TX, transfluthrin (813)+TX,
transpermethrin (1440)+TX, triamiphos (1441)+TX, triazamate
(818)+TX, triazophos (820)+TX, triazuron+TX, trichlorfon (824)+TX,
trichlormetaphos-3 [CCN]+TX, trichloronat (1452)+TX, trifenofos
(1455)+TX, triflumuron (835)+TX, trimethacarb (840)+TX, triprene
(1459)+TX, vamidothion (847)+TX, vaniliprole [CCN]+TX, veratridine
(725)+TX, veratrine (725)+TX, XMC (853)+TX, xylylcarb (854)+TX,
YI-5302 (compound code)+TX, zeta-cypermethrin (205)+TX,
zetamethrin+TX, zinc phosphide (640)+TX, zolaprofos (1469) and ZXI
8901 (development code) (858)+TX, cyantraniliprole
[736994-63-19+TX, chlorantraniliprole [500008-45-7]+TX,
cyenopyrafen [560121-52-0]+TX, cyflumetofen [400882-07-7]+TX,
pyrifluquinazon [337458-27-2]+TX, spinetoram
[187166-40-1+187166-15-0]+TX, spirotetramat [203313-25-1]+TX,
sulfoxaflor [946578-00-3]+TX, flufiprole [704886-18-0]+TX,
meperfluthrin [915288-13-0]+TX, tetramethylfluthrin
[84937-88-2]+TX, triflumezopyrim (disclosed in WO 2012/092115)+TX,
fluxametamide (WO 2007/026965)+TX, epsilon-metofluthrin
[240494-71-7]+TX, epsilon-momfluorothrin [1065124-65-3]+TX,
fluazaindolizine [1254304-22-7]+TX, chloroprallethrin
[399572-87-3]+TX, fluxametamide [928783-29-3]+TX, cyhalodiamide
[1262605-53-7]+TX, tioxazafen [330459-31-9]+TX, broflanilide
[1207727-04-5]+TX, flufiprole [704886-18-0]+TX, cyclaniliprole
[1031756-98-5]+TX, tetraniliprole [1229654-66-3]+TX, guadipyr
(described in WO2010/060231)+TX, cycloxaprid (described in
WO2005/077934)+TX,
a molluscicide selected from the group of substances consisting of
bis(tributyltin) oxide (IUPAC name) (913)+TX, bromoacetamide
[CCN]+TX, calcium arsenate [CCN]+TX, cloethocarb (999)+TX, copper
acetoarsenite [CCN]+TX, copper sulfate (172)+TX, fentin (347)+TX,
ferric phosphate (IUPAC name) (352)+TX, metaldehyde (518)+TX,
methiocarb (530)+TX, niclosamide (576)+TX, niclosamide-olamine
(576)+TX, pentachlorophenol (623)+TX, sodium pentachlorophenoxide
(623)+TX, tazimcarb (1412)+TX, thiodicarb (799)+TX, tributyltin
oxide (913)+TX, trifenmorph (1454)+TX, trimethacarb (840)+TX,
triphenyltin acetate (IUPAC name) (347) and triphenyltin hydroxide
(IUPAC name) (347)+TX, pyriprole [394730-71-3]+TX,
a nematicide selected from the group of substances consisting of
AKD-3088 (compound code)+TX, 1,2-dibromo-3-chloropropane
(IUPAC/Chemical Abstracts name) (1045)+TX, 1,2-dichloropropane
(IUPAC/Chemical Abstracts name) (1062)+TX, 1,2-dichloropropane with
1,3-dichloropropene (IUPAC name) (1063)+TX, 1,3-dichloropropene
(233)+TX, 3,4-dichlorotetrahydrothiophene 1,1-dioxide
(IUPAC/Chemical Abstracts name) (1065)+TX,
3-(4-chlorophenyl)-5-methylrhodanine (IUPAC name) (980)+TX,
5-methyl-6-thioxo-1,3,5-thiadiazinan-3-ylacetic acid (IUPAC name)
(1286)+TX, 6-isopentenylaminopurine (210)+TX, abamectin (1)+TX,
acetoprole [CCN]+TX, alanycarb (15)+TX, aldicarb (16)+TX,
aldoxycarb (863)+TX, AZ 60541 (compound code)+TX, benclothiaz
[CCN]+TX, benomyl (62)+TX, butylpyridaben+TX, cadusafos (109)+TX,
carbofuran (118)+TX, carbon disulfide (945)+TX, carbosulfan
(119)+TX, chloropicrin (141)+TX, chlorpyrifos (145)+TX, cloethocarb
(999)+TX, cytokinins (210)+TX, dazomet (216)+TX, DBCP (1045)+TX,
DCIP (218)+TX, diamidafos (1044)+TX, dichlofenthion (1051)+TX,
dicliphos+TX, dimethoate (262)+TX, doramectin [CCN]+TX, emamectin
(291)+TX, emamectin benzoate (291)+TX, eprinomectin [CCN]+TX,
ethoprophos (312)+TX, ethylene dibromide (316)+TX, fenamiphos
(326)+TX, fenpyrad+TX, fensulfothion (1158)+TX, fosthiazate
(408)+TX, fosthietan (1196)+TX, furfural [CCN]+TX, GY-81
(development code) (423)+TX, heterophos [CCN]+TX, iodomethane
(IUPAC name) (542)+TX, isamidofos (1230)+TX, isazofos (1231)+TX,
ivermectin [CCN]+TX, kinetin (210)+TX, mecarphon (1258)+TX, metam
(519)+TX, metam-potassium (519)+TX, metam-sodium (519)+TX, methyl
bromide (537)+TX, methyl isothiocyanate (543)+TX, milbemycin oxime
[CCN]+TX, moxidectin [CCN]+TX, Myrothecium verrucaria composition
(565)+TX, NC-184 (compound code)+TX, oxamyl (602)+TX, phorate
(636)+TX, phosphamidon (639)+TX, phosphocarb [CCN]+TX, sebufos+TX,
selamectin [CCN]+TX, spinosad (737)+TX, terbam+TX, terbufos
(773)+TX, tetrachlorothiophene (IUPAC/Chemical Abstracts name)
(1422)+TX, thiafenox+TX, thionazin (1434)+TX, triazophos (820)+TX,
triazuron+TX, xylenols [CCN]+TX, YI-5302 (compound code) and zeatin
(210)+TX, fluensulfone [318290-98-1]+TX,
a nitrification inhibitor selected from the group of substances
consisting of potassium ethylxanthate [CCN] and nitrapyrin
(580)+TX,
a plant activator selected from the group of substances consisting
of acibenzolar (6)+TX, acibenzolar-S-methyl (6)+TX, probenazole
(658) and Reynoutria sachalinensis extract (720)+TX,
a rodenticide selected from the group of substances consisting of
2-isovalerylindan-1,3-dione (IUPAC name) (1246)+TX,
4-(quinoxalin-2-ylamino)benzenesulfonamide (IUPAC name) (748)+TX,
alpha-chlorohydrin [CCN]+TX, aluminium phosphide (640)+TX, antu
(880)+TX, arsenous oxide (882)+TX, barium carbonate (891)+TX,
bisthiosemi (912)+TX, brodifacoum (89)+TX, bromadiolone (91)+TX,
bromethalin (92)+TX, calcium cyanide (444)+TX, chloralose (127)+TX,
chlorophacinone (140)+TX, cholecalciferol (850)+TX, coumachlor
(1004)+TX, coumafuryl (1005)+TX, coumatetralyl (175)+TX, crimidine
(1009)+TX, difenacoum (246)+TX, difethialone (249)+TX, diphacinone
(273)+TX, ergocalciferol (301)+TX, flocoumafen (357)+TX,
fluoroacetamide (379)+TX, flupropadine (1183)+TX, flupropadine
hydrochloride (1183)+TX, gamma-HCH (430)+TX, HCH (430)+TX, hydrogen
cyanide (444)+TX, iodomethane (IUPAC name) (542)+TX, lindane
(430)+TX, magnesium phosphide (IUPAC name) (640)+TX, methyl bromide
(537)+TX, norbormide (1318)+TX, phosacetim (1336)+TX, phosphine
(IUPAC name) (640)+TX, phosphorus [CCN]+TX, pindone (1341)+TX,
potassium arsenite [CCN]+TX, pyrinuron (1371)+TX, scilliroside
(1390)+TX, sodium arsenite [CCN]+TX, sodium cyanide (444)+TX,
sodium fluoro-acetate (735)+TX, strychnine (745)+TX, thallium
sulfate [CCN]+TX, warfarin (851) and zinc phosphide (640)+TX,
a synergist selected from the group of substances consisting of
2-(2-butoxyethoxy)ethyl piperonylate (IUPAC name) (934)+TX,
5-(1,3-benzodioxol-5-yl)-3-hexylcyclohex-2-enone (IUPAC name)
(903)+TX, farnesol with nerolidol (324)+TX, MB-599 (development
code) (498)+TX, MGK 264 (development code) (296)+TX, piperonyl
butoxide (649)+TX, piprotal (1343)+TX, propyl isomer (1358)+TX,
S421 (development code) (724)+TX, sesamex (1393)+TX, sesasmolin
(1394) and sulfoxide (1406)+TX,
an animal repellent selected from the group of substances
consisting of anthraquinone (32)+TX, chloralose (127)+TX, copper
naphthenate [CCN]+TX, copper oxychloride (171)+TX, diazinon
(227)+TX, dicyclopentadiene (chemical name) (1069)+TX, guazatine
(422)+TX, guazatine acetates (422)+TX, methiocarb (530)+TX,
pyridin-4-amine (IUPAC name) (23)+TX, thiram (804)+TX, trimethacarb
(840)+TX, zinc naphthenate [CCN] and ziram (856)+TX,
a virucide selected from the group of substances consisting of
imanin [CCN] and ribavirin [CCN]+TX, a wound protectant selected
from the group of substances consisting of mercuric oxide (512)+TX,
octhilinone (590) and thiophanate-methyl (802)+TX,
and biologically active compounds selected from the group
consisting of azaconazole (60207-31-0]+TX, bitertanol
[70585-36-3]+TX, bromuconazole [116255-48-2]+TX, cyproconazole
[94361-06-5]+TX, difenoconazole [119446-68-3]+TX, diniconazole
[83657-24-3]+TX, epoxiconazole [106325-08-0]+TX, fenbuconazole
[114369-43-6]+TX, fluquinconazole [136426-54-5]+TX, flusilazole
[85509-19-9]+TX, flutriafol [76674-21-0]+TX, hexaconazole
[79983-71-4]+TX, imazalil [35554-44-0]+TX, imibenconazole
[86598-92-7]+TX, ipconazole [125225-28-7]+TX, metconazole
[125116-23-6]+TX, myclobutanil [88671-89-0]+TX, pefurazoate
[101903-30-4]+TX, penconazole [66246-88-6]+TX, prothioconazole
[178928-70-6]+TX, pyrifenox [88283-41-4]+TX, prochloraz
[67747-09-5]+TX, propiconazole [60207-90-1]+TX, simeconazole
[149508-90-7]+TX, tebuconazole [107534-96-3]+TX, tetraconazole
[112281-77-3]+TX, triadimefon [43121-43-3]+TX, triadimenol
[55219-65-3]+TX, triflumizole [99387-89-0]+TX, triticonazole
[131983-72-7]+TX, ancymidol [12771-68-5]+TX, fenarimol
[60168-88-9]+TX, nuarimol [63284-71-9]+TX, bupirimate
[41483-43-6]+TX, dimethirimol [5221-53-4]+TX, ethirimol
[23947-60-6]+TX, dodemorph [1593-77-7]+TX, fenpropidine
[67306-00-7]+TX, fenpropimorph [67564-91-4]+TX, spiroxamine
[118134-30-8]+TX, tridemorph [81412-43-3]+TX, cyprodinil
[121552-61-2]+TX, mepanipyrim [110235-47-7]+TX, pyrimethanil
[53112-28-0]+TX, fenpiclonil [74738-17-3]+TX, fludioxonil
[131341-86-1]+TX, benalaxyl [71626-11-4]+TX, furalaxyl
[57646-30-7]+TX, metalaxyl [57837-19-1]+TX, R-metalaxyl
[70630-17-0]+TX, ofurace [58810-48-3]+TX, oxadixyl [77732-09-3]+TX,
benomyl [17804-35-2]+TX, carbendazim [10605-21-7]+TX, debacarb
[62732-91-6]+TX, fuberidazole [3878-19-1]+TX, thiabendazole
[148-79-8]+TX, chlozolinate [84332-86-5]+TX, dichlozoline
[24201-58-9]+TX, iprodione [36734-19-7]+TX, myclozoline
[54864-61-8]+TX, procymidone [32809-16-8]+TX, vinclozoline
[50471-44-8]+TX, boscalid [188425-85-6]+TX, carboxin
[5234-68-4]+TX, fenfuram [24691-80-3]+TX, flutolanil
[66332-96-5]+TX, mepronil [55814-41-0]+TX, oxycarboxin
[5259-88-1]+TX, penthiopyrad [183675-82-3]+TX, thifluzamide
[130000-40-7]+TX, guazatine [108173-90-6]+TX, dodine [2439-10-3]
[112-65-2] (free base)+TX, iminoctadine [13516-27-3]+TX,
azoxystrobin [131860-33-8]+TX, dimoxystrobin [149961-52-4]+TX,
enestroburin {Proc. BCPC, Int. Congr., Glasgow, 2003, 1, 93}+TX,
fluoxastrobin [361377-29-9]+TX, kresoxim-methyl [143390-89-0]+TX,
metominostrobin [133408-50-1]+TX, trifloxystrobin [141517-21-7]+TX,
orysastrobin [248593-16-0]+TX, picoxystrobin [117428-22-5]+TX,
pyraclostrobin [175013-18-0]+TX, ferbam [14484-64-1]+TX, mancozeb
[8018-01-7]+TX, maneb [12427-38-2]+TX, metiram [9006-42-2]+TX,
propineb [12071-83-9]+TX, thiram [137-26-8]+TX, zineb
[12122-67-7]+TX, ziram [137-30-4]+TX, captafol [2425-06-1]+TX,
captan [133-06-2]+TX, dichlofluanid [1085-98-9]+TX, fluoroimide
[41205-21-4]+TX, folpet [133-07-3]+TX, tolylfluanid [731-27-1]+TX,
bordeaux mixture [8011-63-0]+TX, copperhydroxid [20427-59-2]+TX,
copperoxychlorid [1332-40-7]+TX, coppersulfat [7758-98-7]+TX,
copperoxid [1317-39-1]+TX, mancopper [53988-93-5]+TX, oxine-copper
[10380-28-6]+TX, dinocap [131-72-6]+TX, nitrothal-isopropyl
[10552-74-6]+TX, edifenphos [17109-49-8]+TX, iprobenphos
[26087-47-8]+TX, isoprothiolane [50512-35-1]+TX, phosdiphen
[36519-00-3]+TX, pyrazophos [13457-18-6]+TX, tolclofos-methyl
[57018-04-9]+TX, acibenzolar-S-methyl [135158-54-2]+TX, anilazine
[101-05-3]+TX, benthiavalicarb [413615-35-7]+TX, blasticidin-S
[2079-00-7]+TX, chinomethionat [2439-01-2]+TX, chloroneb
[2675-77-6]+TX, chlorothalonil [1897-45-6]+TX, cyflufenamid
[180409-60-3]+TX, cymoxanil [57966-95-7]+TX, dichlone
[117-80-6]+TX, diclocymet [139920-32-4]+TX, diclomezine
[62865-36-5]+TX, dicloran [99-30-9]+TX, diethofencarb
[87130-20-9]+TX, dimethomorph [110488-70-5]+TX, SYP-LI90 (Flumorph)
[211867-47-9]+TX, dithianon [3347-22-6]+TX, ethaboxam
[162650-77-3]+TX, etridiazole [2593-15-9]+TX, famoxadone
[131807-57-3]+TX, fenamidone [161326-34-7]+TX, fenoxanil
[115852-48-7]+TX, fentin [668-34-8]+TX, ferimzone [89269-64-7]+TX,
fluazinam [79622-59-6]+TX, fluopicolide [239110-15-7]+TX,
flusulfamide [106917-52-6]+TX, fenhexamid [126833-17-8]+TX,
fosetyl-aluminium [39148-24-8]+TX, hymexazol [10004-44-1]+TX,
iprovalicarb [140923-17-7]+TX, IKF-916 (Cyazofamid)
[120116-88-3]+TX, kasugamycin [6980-18-3]+TX, methasulfocarb
[66952-49-6]+TX, metrafenone [220899-03-6]+TX, pencycuron
[66063-05-6]+TX, phthalide [27355-22-2]+TX, polyoxins
[11113-80-7]+TX, probenazole [27605-76-1]+TX, propamocarb
[25606-41-1]+TX, proquinazid [189278-12-4]+TX, pyroquilon
[57369-32-1]+TX, quinoxyfen [124495-18-7]+TX, quintozene
[82-68-8]+TX, sulfur [7704-34-9]+TX, tiadinil [223580-51-6]+TX,
triazoxide [72459-58-6]+TX, tricyclazole [41814-78-2]+TX, triforine
[26644-46-2]+TX, validamycin [37248-47-8]+TX, zoxamide (RH7281)
[156052-68-5]+TX, mandipropamid [374726-62-2]+TX, isopyrazam
[881685-58-1]+TX, sedaxane [874967-67-6]+TX,
3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid
(9-dichloromethylene-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-yl)-amid-
e (dislosed in WO 2007/048556)+TX,
3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid
(3',4',5'-trifluoro-biphenyl-2-yl)-amide (disclosed in WO
2006/087343)+TX,
[(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-3-[(cyclopropylcarbonyl)oxy]-1,3,4,4a,5-
,6,6a,12,12a,12b-decahydro-6,12-dihydroxy-4,6a,12b-trimethyl-11-oxo-9-(3-p-
yridinyl)-2H,11Hnaphtho[2,1-b]pyrano[3,4-e]pyran-4-yl]methyl-cyclopropanec-
arboxylate [915972-17-7]+TX and
1,3,5-trimethyl-N-(2-methyl-1-oxopropyl)-N-[3-(2-methylpropyl)-4-[2,2,2-t-
rifluoro-1-methoxy-1-(trifluoromethyl)ethyl]phenyl]-1H-pyrazole-4-carboxam-
ide [926914-55-8]+TX; and
microbials including: Acinetobacter Iwoffii+TX, Acremonium
alternatum+TX+TX, Acremonium cephalosporium+TX+TX, Acremonium
diospyri+TX, Acremonium obclavatum+TX, Adoxophyes orana
granulovirus (AdoxGV) (Capex.RTM.)+TX, Agrobacterium radiobacter
strain K84 (Galltrol-A.RTM.)+TX, Alternaria alternate+TX,
Alternaria cassia+TX, Alternaria destruens (Smolder.RTM.)+TX,
Ampelomyces quisqualis (AQ10.RTM.)+TX, Aspergillus flavus AF36
(AF36.RTM.)+TX, Aspergillus flavus NRRL 21882 (Aflaguard.RTM.)+TX,
Aspergillus spp.+TX, Aureobasidium pullulans+TX, Azospirillum+TX,
(MicroAZ.RTM.+TX, TAZO B.RTM.)+TX, Azotobacter+TX, Azotobacter
chroocuccum (Azotomeal.RTM.)+TX, Azotobacter cysts (Bionatural
Blooming Blossoms.RTM.)+TX, Bacillus amyloliquefaciens+TX, Bacillus
cereus+TX, Bacillus chitinosporus strain CM-1+TX, Bacillus
chitinosporus strain AQ746+TX, Bacillus licheniformis strain HB-2
(Biostart.TM. Rhizoboost.RTM.)+TX, Bacillus licheniformis strain
3086 (EcoGuard.RTM.+TX, Green Releaf.RTM.)+TX, Bacillus
circulans+TX, Bacillus firmus (BioSafe.RTM.+TX, BioNem-WP.RTM.+TX,
VOTiVO.RTM.)+TX, Bacillus firmus strain 1-1582+TX, Bacillus
macerans+TX, Bacillus marismortui+TX, Bacillus megaterium+TX,
Bacillus mycoides strain AQ726+TX, Bacillus papillae (Milky Spore
Powder.RTM.)+TX, Bacillus pumilus spp.+TX, Bacillus pumilus strain
GB34 (Yield Shield.RTM.)+TX, Bacillus pumilus strain AQ717+TX,
Bacillus pumilus strain QST 2808 (Sonata.RTM.+TX, Ballad
Plus.RTM.)+TX, Bacillus spahericus (VectoLex.RTM.)+TX, Bacillus
spp.+TX, Bacillus spp. strain AQ175+TX, Bacillus spp. strain
AQ177+TX, Bacillus spp. strain AQ178+TX, Bacillus subtilis strain
QST 713 (CEASE.RTM.+TX, Serenade.RTM.+TX, Rhapsody.RTM.)+TX,
Bacillus subtilis strain QST 714 (JAZZ.RTM.)+TX, Bacillus subtilis
strain AQ153+TX, Bacillus subtilis strain AQ743+TX, Bacillus
subtilis strain QST3002+TX, Bacillus subtilis strain QST3004+TX,
Bacillus subtilis var. amyloliquefaciens strain FZB24
(Taegro.RTM.+TX, Rhizopro.RTM.)+TX, Bacillus thuringiensis Cry
2Ae+TX, Bacillus thuringiensis Cry1 Ab+TX, Bacillus thuringiensis
aizawai GC 91 (Agree.RTM.)+TX, Bacillus thuringiensis israelensis
(BMP123.RTM.+TX, Aquabac.RTM.+TX, VectoBac.RTM.)+TX, Bacillus
thuringiensis kurstaki (Javelin.RTM.+TX, Deliver.RTM.+TX,
CryMax.RTM.+TX, Bonide.RTM.+TX, Scutella WP.RTM.+TX, Turilav
WP.RTM.+TX, Astuto.RTM.+TX, Dipel WP.RTM.+TX, Biobit.RTM.+TX,
Foray.RTM.)+TX, Bacillus thuringiensis kurstaki BMP 123
(Baritone.RTM.)+TX, Bacillus thuringiensis kurstaki HD-1
(Bioprotec-CAF/3P.RTM.)+TX, Bacillus thuringiensis strain BD#32+TX,
Bacillus thuringiensis strain AQ52+TX, Bacillus thuringiensis var.
aizawai (XenTari.RTM.+TX, DiPel.RTM.)+TX, bacteria spp.
(GROWMEND.RTM.+TX, GROWSWEET.RTM.+TX, Shootup.RTM.)+TX,
bacteriophage of Clavipacter michiganensis (AgriPhage.RTM.)+TX,
Bakflor.RTM.+TX, Beauveria bassiana (Beaugenic.RTM.+TX, Brocaril
WP.RTM.)+TX, Beauveria bassiana GHA (Mycotrol ES.RTM.+TX, Mycotrol
O.RTM.+TX, BotaniGuard.RTM.)+TX, Beauveria brongniartii
(Engerlingspilz.RTM.+TX, Schweizer Beauveria.RTM.+TX,
Melocont.RTM.)+TX, Beauveria spp.+TX, Botrytis cineria+TX,
Bradyrhizobium japonicum (TerraMax.RTM.)+TX, Brevibacillus
brevis+TX, Bacillus thuringiensis tenebrionis (Novodor.RTM.)+TX,
BtBooster+TX, Burkholderia cepacia (Deny.RTM.+TX,
Intercept.RTM.+TX, Blue Circle.RTM.)+TX, Burkholderia gladii+TX,
Burkholderia gladioli+TX, Burkholderia spp.+TX, Canadian thistle
fungus (CBH Canadian Bioherbicide.RTM.)+TX, Candida butyri+TX,
Candida famata+TX, Candida fructus+TX, Candida glabrata+TX, Candida
guilliermondii+TX, Candida melibiosica+TX, Candida oleophila strain
O+TX, Candida parapsilosis+TX, Candida pelliculosa+TX, Candida
pulcherrima+TX, Candida reukaufii+TX, Candida saitoana
(Bio-Coat.RTM.+TX, Biocure.RTM.)+TX, Candida sake+TX, Candida
spp.+TX, Candida tenius+TX, Cedecea dravisae+TX, Cellulomonas
flavigena+TX, Chaetomium cochliodes (Nova-Cide.RTM.)+TX, Chaetomium
globosum (Nova-Cide.RTM.)+TX, Chromobacterium subtsugae strain
PRAA4-1T (Grandevo.RTM.)+TX, Cladosporium cladosporioides+TX,
Cladosporium oxysporum+TX, Cladosporium chlorocephalum+TX,
Cladosporium spp.+TX, Cladosporium tenuissimum+TX, Clonostachys
rosea (EndoFine.RTM.)+TX, Colletotrichum acutatum+TX, Coniothyrium
minitans (Cotans WG.RTM.)+TX, Coniothyrium spp.+TX, Cryptococcus
albidus (YIELDPLUS.RTM.)+TX, Cryptococcus humicola+TX, Cryptococcus
infirmo-miniatus+TX, Cryptococcus laurentii+TX, Cryptophlebia
leucotreta granulovirus (Cryptex.RTM.)+TX, Cupriavidus
campinensis+TX, Cydia pomonella granulovirus (CYD-X.RTM.)+TX, Cydia
pomonella granulovirus (Madex.RTM.+TX, Madex Plus.RTM.+TX, Madex
Max/Carpovirusine.RTM.)+TX, Cylindrobasidium laeve
(Stumpout.RTM.)+TX, Cylindrocladium+TX, Debaryomyces hansenii+TX,
Drechslera hawaiinensis+TX, Enterobacter cloacae+TX,
Enterobacteriaceae+TX, Entomophtora virulenta (Vektor.RTM.)+TX,
Epicoccum nigrum+TX, Epicoccum purpurascens+TX, Epicoccum spp.+TX,
Filobasidium floriforme+TX, Fusarium acuminatum+TX, Fusarium
chlamydosporum+TX, Fusarium oxysporum (Fusaclean.RTM./Biofox
C.RTM.)+TX, Fusarium proliferatum+TX, Fusarium spp.+TX,
Galactomyces geotrichum+TX, Gliocladium catenulatum
(Primastop.RTM.+TX, Prestop.RTM.)+TX, Gliocladium roseum+TX,
Gliocladium spp. (SoilGard.RTM.)+TX, Gliocladium virens
(Soilgard.RTM.)+TX, Granulovirus (Granupom.RTM.)+TX, Halobacillus
halophilus+TX, Halobacillus litoralis+TX, Halobacillus trueperi+TX,
Halomonas spp.+TX, Halomonas subglaciescola+TX, Halovibrio
variabilis+TX, Hanseniaspora uvarum+TX, Helicoverpa armigera
nucleopolyhedrovirus (Helicovex.RTM.)+TX, Helicoverpa zea nuclear
polyhedrosis virus (Gemstar.RTM.)+TX, Isoflavone--formononetin
(Myconate.RTM.)+TX, Kloeckera apiculata+TX, Kloeckera spp.+TX,
Lagenidium giganteum (Laginex.RTM.)+TX, Lecanicillium longisporum
(Vertiblast.RTM.)+TX, Lecanicillium muscarium (Vertikil.RTM.)+TX,
Lymantria Dispar nucleopolyhedrosis virus (Disparvirus.RTM.)+TX,
Marinococcus halophilus+TX, Meira geulakonigi+TX, Metarhizium
anisopliae (Met52.RTM.)+TX, Metarhizium anisopliae (Destruxin
WP.RTM.)+TX, Metschnikowia fruticola (Shemer.RTM.)+TX,
Metschnikowia pulcherrima+TX, Microdochium dimerum
(Antibot.RTM.)+TX, Micromonospora coerulea+TX, Microsphaeropsis
ochracea+TX, Muscodor albus 620 (Muscudor.RTM.)+TX, Muscodor roseus
strain A3-5+TX, Mycorrhizae spp. (AMykor.RTM.+TX, Root
Maximizer.RTM.)+TX, Myrothecium verrucaria strain AARC-0255
(DiTera.RTM.)+TX, BROS PLUS.RTM.+TX, Ophiostoma piliferum strain
D97 (Sylvanex.RTM.)+TX, Paecilomyces farinosus+TX, Paecilomyces
fumosoroseus (PFR-97.RTM.+TX, PreFeRal.RTM.)+TX, Paecilomyces
linacinus (Biostat WP.RTM.)+TX, Paecilomyces lilacinus strain 251
(MeloCon WG.RTM.)+TX, Paenibacillus polymyxa+TX, Pantoea
agglomerans (BlightBan C9-1.RTM.)+TX, Pantoea spp.+TX, Pasteuria
spp. (Econem.RTM.)+TX, Pasteuria nishizawae+TX, Penicillium
aurantiogriseum+TX, Penicillium billai (Jumpstart.RTM.+TX,
TagTeam.RTM.)+TX, Penicillium brevicompactum+TX, Penicillium
frequentans+TX, Penicillium griseofulvum+TX, Penicillium
purpurogenum+TX, Penicillium spp.+TX, Penicillium viridicatum+TX,
Phlebiopsis gigantean (Rotstop.RTM.)+TX, phosphate solubilizing
bacteria (Phosphomeal.RTM.)+TX, Phytophthora cryptogea+TX,
Phytophthora palmivora (Devine.RTM.)+TX, Pichia anomala+TX, Pichia
guilermondii+TX, Pichia membranaefaciens+TX, Pichia onychis+TX,
Pichia stipites+TX, Pseudomonas aeruginosa+TX, Pseudomonas
aureofasciens (Spot-Less Biofungicide.RTM.)+TX, Pseudomonas
cepacia+TX, Pseudomonas chlororaphis (AtEze.RTM.)+TX, Pseudomonas
corrugate+TX, Pseudomonas fluorescens strain A506 (BlightBan
A506.RTM.)+TX, Pseudomonas putida+TX, Pseudomonas reactans+TX,
Pseudomonas spp.+TX, Pseudomonas syringae (Bio-Save.RTM.)+TX,
Pseudomonas viridiflava+TX, Pseudomons fluorescens (Zequanox)+TX,
Pseudozyma flocculosa strain PF-A22 UL (Sporodex L.RTM.)+TX,
Puccinia canaliculata+TX, Puccinia thlaspeos (Wood
Warrior.RTM.)+TX, Pythium paroecandrum+TX, Pythium oligandrum
(Polygandron.RTM.+TX, Polyversum.RTM.)+TX, Pythium periplocum+TX,
Rhanella aquatilis+TX, Rhanella spp.+TX, Rhizobia (Dormal.RTM.+TX,
Vault.RTM.)+TX, Rhizoctonia+TX, Rhodococcus globerulus strain
AQ719+TX, Rhodosporidium diobovatum+TX, Rhodosporidium
toruloides+TX, Rhodotorula spp.+TX, Rhodotorula glutinis+TX,
Rhodotorula graminis+TX, Rhodotorula mucilagnosa+TX, Rhodotorula
rubra+TX, Saccharomyces cerevisiae+TX, Salinococcus roseus+TX,
Sclerotinia minor+TX, Sclerotinia minor (SARRITOR.RTM.)+TX,
Scytalidium spp.+TX, Scytalidium uredinicola+TX, Spodoptera exigua
nuclear polyhedrosis virus (Spod-X.RTM.+TX, Spexit.RTM.)+TX,
Serratia marcescens+TX, Serratia plymuthica+TX, Serratia spp.+TX,
Sordaria fimicola+TX, Spodoptera littoralis nucleopolyhedrovirus
(Littovir.RTM.)+TX, Sporobolomyces roseus+TX, Stenotrophomonas
maltophilia+TX, Streptomyces ahygroscopicus+TX, Streptomyces
albaduncus+TX, Streptomyces exfoliates+TX, Streptomyces galbus+TX,
Streptomyces griseoplanus+TX, Streptomyces griseoviridis
(Mycostop.RTM.)+TX, Streptomyces lydicus (Actinovate.RTM.)+TX,
Streptomyces lydicus WYEC-108 (ActinoGrow.RTM.)+TX, Streptomyces
violaceus+TX, Tilletiopsis minor+TX, Tilletiopsis spp.+TX,
Trichoderma asperellum (T34 Biocontrol.RTM.)+TX, Trichoderma gamsii
(Tenet.RTM.)+TX, Trichoderma atroviride (Plantmate.RTM.)+TX,
Trichoderma hamatum TH 382+TX, Trichoderma harzianum rifai
(Mycostar.RTM.)+TX, Trichoderma harzianum T-22 (Trianum-P.RTM.+TX,
PlantShield HC.RTM.+TX, RootShield.RTM.+TX, Trianum-G.RTM.)+TX,
Trichoderma harzianum T-39 (Trichodex.RTM.)+TX, Trichoderma
inhamatum+TX, Trichoderma koningii+TX, Trichoderma spp. LC 52
(Sentinel.RTM.)+TX, Trichoderma lignorum+TX, Trichoderma
longibrachiatum+TX, Trichoderma polysporum (Binab T.RTM.)+TX,
Trichoderma taxi+TX, Trichoderma virens+TX, Trichoderma virens
(formerly Gliocladium virens GL-21) (SoilGuard.RTM.)+TX,
Trichoderma viride+TX, Trichoderma viride strain ICC 080
(Remedier.RTM.)+TX, Trichosporon pullulans+TX, Trichosporon
spp.+TX, Trichothecium spp.+TX, Trichothecium roseum+TX, Typhula
phacorrhiza strain 94670+TX, Typhula phacorrhiza strain 94671+TX,
Ulocladium atrum+TX, Ulocladium oudemansii (Botry-Zen.RTM.)+TX,
Ustilago maydis+TX, various bacteria and supplementary
micronutrients (Natural II.RTM.)+TX, various fungi (Millennium
Microbes.RTM.)+TX, Verticillium chlamydosporium+TX, Verticillium
lecanii (Mycotal.RTM.+TX, Vertalec.RTM.)+TX, Vip3Aa20
(VIPtera.RTM.)+TX, Virgibaclillus marismortui+TX, Xanthomonas
campestris pv. Poae (Camperico.RTM.)+TX, Xenorhabdus bovienii+TX,
Xenorhabdus nematophilus; and
Plant extracts including: pine oil (Retenol.RTM.)+TX, azadirachtin
(Plasma Neem Oil.RTM.+TX, AzaGuard.RTM.+TX, MeemAzal.RTM.+TX,
Molt-X.RTM.+TX, Botanical IGR (Neemazad.RTM.+TX, Neemix.RTM.)+TX,
canola oil (Lilly Miller Vegol.RTM.)+TX, Chenopodium ambrosioides
near ambrosioides (Requiem.RTM.)+TX, Chrysanthemum extract
(Crisant.RTM.)+TX, extract of neem oil (Trilogy.RTM.)+TX,
essentials oils of Labiatae (Botania.RTM.)+TX, extracts of clove
rosemary peppermint and thyme oil (Garden insect Killer.RTM.)+TX,
Glycinebetaine (Greenstim.RTM.)+TX, garlic+TX, lemongrass oil
(GreenMatch.RTM.)+TX, neem oil+TX, Nepeta cataria (Catnip oil)+TX,
Nepeta catarina+TX, nicotine+TX, oregano oil (MossBuster.RTM.)+TX,
Pedaliaceae oil (Nematon.RTM.)+TX, pyrethrum+TX, Quillaja saponaria
(NemaQ.RTM.)+TX, Reynoutria sachalinensis (Regalia.RTM.+TX,
Sakalia.RTM.)+TX, rotenone (Eco Roten.RTM.)+TX, Rutaceae plant
extract (Soleo.RTM.)+TX, soybean oil (Ortho Ecosense.RTM.)+TX, tea
tree oil (Timorex Gold.RTM.)+TX, thymus oil+TX, AGNIQUE.RTM.
MMF+TX, BugOil.RTM.+TX, mixture of rosemary sesame pepermint thyme
and cinnamon extracts (EF 300.RTM.)+TX, mixture of clove rosemary
and peppermint extract (EF 400.RTM.)+TX, mixture of clove pepermint
garlic oil and mint (Soil Shot.RTM.)+TX, kaolin (Screen.RTM.)+TX,
storage glucam of brown algae (Laminarin.RTM.); and
pheromones including: blackheaded fireworm pheromone (3M Sprayable
Blackheaded Fireworm Pheromone.RTM.)+TX, Codling Moth Pheromone
(Paramount dispenser-(CM)/Isomate C-Plus.RTM.)+TX, Grape Berry Moth
Pheromone (3M MEC-GBM Sprayable Pheromone.RTM.)+TX, Leafroller
pheromone (3M MEC--LR Sprayable Pheromone.RTM.)+TX, Muscamone
(Snip7 Fly Bait.RTM.+TX, Starbar Premium Fly Bait.RTM.)+TX,
Oriental Fruit Moth Pheromone (3M oriental fruit moth sprayable
Pheromone.RTM.)+TX, Peachtree Borer Pheromone (Isomate-P.RTM.)+TX,
Tomato Pinworm Pheromone (3M Sprayable Pheromone.RTM.)+TX, Entostat
powder (extract from palm tree) (Exosex CM.RTM.)+TX,
(E+TX,Z+TX,Z)-3+TX,8+TX,11 Tetradecatrienyl acetate+TX,
(Z+TX,Z+TX,E)-7+TX,11+TX,13-Hexadecatrienal+TX,
(E+TX,Z)-7+TX,9-Dodecadien-1-yl acetate+TX, 2-Methyl-1-butanol+TX,
Calcium acetate+TX, Scenturion.RTM.+TX, Biolure.RTM.+TX,
Check-Mate.RTM.+TX, Lavandulyl senecioate; and Macrobials
including: Aphelinus abdominalis+TX, Aphidius ervi
(Aphelinus-System.RTM.)+TX, Acerophagus papaya+TX, Adalia
bipunctata (Adalia-System.RTM.)+TX, Adalia bipunctata
(Adaline.RTM.)+TX, Adalia bipunctata (Aphidalia.RTM.)+TX,
Ageniaspis citricola+TX, Ageniaspis fuscicollis+TX, Amblyseius
andersoni (Anderline.RTM.+TX, Andersoni-System.RTM.)+TX, Amblyseius
californicus (Amblyline.RTM.+TX, Spical.RTM.)+TX, Amblyseius
cucumeris (Thripex.RTM.+TX, Bugline Cucumeris.RTM.)+TX, Amblyseius
fallacis (Fallacis.RTM.)+TX, Amblyseius swirskii (Bugline
Swirskii.RTM.+TX, Swirskii-Mite.RTM.)+TX, Amblyseius womersleyi
(WomerMite.RTM.)+TX, Amitus hesperidum+TX, Anagrus atomus+TX,
Anagyrus fusciventris+TX, Anagyrus kamali+TX, Anagyrus loecki+TX,
Anagyrus pseudococci (Citripar.RTM.)+TX, Anicetus benefices+TX,
Anisopteromalus calandrae+TX, Anthocoris nemoralis
(Anthocoris-System.RTM.)+TX, Aphelinus abdominalis
(Apheline.RTM.+TX, Aphiline.RTM.)+TX, Aphelinus asychis+TX,
Aphidius colemani (Aphipar.RTM.)+TX, Aphidius ervi
(Ervipar.RTM.)+TX, Aphidius gifuensis+TX, Aphidius matricariae
(Aphipar-M.RTM.)+TX, Aphidoletes aphidimyza (Aphidend.RTM.)+TX,
Aphidoletes aphidimyza (Aphidoline.RTM.)+TX, Aphytis
lingnanensis+TX, Aphytis melinus+TX, Aprostocetus hagenowii+TX,
Atheta coriaria (Staphyline.RTM.)+TX, Bombus spp.+TX, Bombus
terrestris (Natupol Beehive.RTM.)+TX, Bombus terrestris
(Beeline.RTM.+TX, Tripol.RTM.)+TX, Cephalonomia stephanoderis+TX,
Chilocorus nigritus+TX, Chrysoperla camea (Chrysoline.RTM.)+TX,
Chrysoperla carnea (Chrysopa.RTM.)+TX, Chrysoperla rufilabris+TX,
Cirrospilus ingenuus+TX, Cirrospilus quadristriatus+TX,
Citrostichus phyllocnistoides+TX, Closterocerus chamaeleon+TX,
Closterocerus spp.+TX, Coccidoxenoides perminutus
(Planopar.RTM.)+TX, Coccophagus cowperi+TX, Coccophagus
lycimnia+TX, Cotesia flavipes+TX, Cotesia plutellae+TX,
Cryptolaemus montrouzieri (Cryptobug.RTM.+TX, Cryptoline.RTM.)+TX,
Cybocephalus nipponicus+TX, Dacnusa sibirica+TX, Dacnusa sibirica
(Minusa.RTM.)+TX, Diglyphus isaea (Diminex.RTM.)+TX, Delphastus
catalinae (Delphastus.RTM.)+TX, Delphastus pusillus+TX,
Diachasmimorpha krausii+TX, Diachasmimorpha longicaudata+TX,
Diaparsis jucunda+TX, Diaphorencyrtus aligarhensis+TX, Diglyphus
isaea+TX, Diglyphus isaea (Miglyphus.RTM.+TX, Digline.RTM.)+TX,
Dacnusa sibirica (DacDigline.RTM.+TX, Minex.RTM.)+TX, Diversinervus
spp.+TX, Encarsia citrina+TX, Encarsia formosa (Encarsia
Max.RTM.+TX, Encarline.RTM.+TX, En-Strip.RTM.)+TX, Eretmocerus
eremicus (Enermix.RTM.)+TX, Encarsia guadeloupae+TX, Encarsia
haitiensis+TX, Episyrphus balteatus (Syrphidend.RTM.)+TX,
Eretmoceris siphonini+TX, Eretmocerus californicus+TX, Eretmocerus
eremicus (Ercal.RTM.+TX, Eretline e.RTM.)+TX, Eretmocerus eremicus
(Bemimix.RTM.)+TX, Eretmocerus hayati+TX, Eretmocerus mundus
(Bemipar.RTM.+TX, Eretline m.RTM.)+TX, Eretmocerus siphonini+TX,
Exochomus quadripustulatus+TX, Feltiella acarisuga
(Spidend.RTM.)+TX, Feltiella acarisuga (Feltiline.RTM.)+TX, Fopius
arisanus+TX, Fopius ceratitivorus+TX, Formononetin (Wirless
Beehome.RTM.)+TX, Franklinothrips vespiformis (Vespop.RTM.)+TX,
Galendromus occidentalis+TX, Goniozus legneri+TX, Habrobracon
hebetor+TX, Harmonia axyridis (HarmoBeetle.RTM.)+TX,
Heterorhabditis spp. (Lawn Patrol.RTM.)+TX, Heterorhabditis
bacteriophora (NemaShield HB.RTM.+TX, Nemaseek.RTM.+TX,
Terranem-Nam.RTM.+TX, Terranem.RTM.+TX, Larvanem.RTM.+TX,
B-Green.RTM.+TX, NemAttack.RTM.+TX, Nematop.RTM.)+TX,
Heterorhabditis megidis (Nemasys H.RTM.+TX, BioNem H.RTM.+TX,
Exhibitline hm.RTM.+TX, Larvanem-M.RTM.)+TX, Hippodamia
convergens+TX, Hypoaspis aculeifer (Aculeifer-System.RTM.+TX,
Entomite-A.RTM.)+TX, Hypoaspis miles (Hypoline m.RTM.+TX,
Entomite-M.RTM.)+TX, Lbalia leucospoides+TX, Lecanoideus
floccissimus+TX, Lemophagus errabundus+TX, Leptomastidea
abnormis+TX, Leptomastix dactylopii (Leptopar.RTM.)+TX, Leptomastix
epona+TX, Lindorus lophanthae+TX, Lipolexis oregmae+TX, Lucilia
caesar (Natufly.RTM.)+TX, Lysiphlebus testaceipes+TX, Macrolophus
caliginosus (Mirical-N.RTM.+TX, Macroline c.RTM..RTM.+TX,
Mirical.RTM.)+TX, Mesoseiulus longipes+TX, Metaphycus flavus+TX,
Metaphycus lounsburyi+TX, Micromus angulatus (Milacewing.RTM.)+TX,
Microterys flavus+TX, Muscidifurax raptorellus and Spalangia
cameroni (Biopar.RTM.)+TX, Neodryinus typhlocybae+TX, Neoseiulus
californicus+TX, Neoseiulus cucumeris (THRYPEX.RTM.)+TX, Neoseiulus
fallacis+TX, Nesideocoris tenuis (NesidioBug.RTM.+TX,
Nesibug.RTM.)+TX, Ophyra aenescens (Biofly.RTM.)+TX, Orius
insidiosus (Thripor-I.RTM.+TX, Oriline i.RTM.)+TX, Orius laevigatus
(Thripor-L.RTM.+TX, Oriline I.RTM.)+TX, Orius majusculus (Oriline
m.RTM.)+TX, Orius strigicollis (Thripor-S.RTM.)+TX, Pauesia
juniperorum+TX, Pediobius foveolatus+TX, Phasmarhabditis
hermaphrodita (Nemaslug.RTM.)+TX, Phymastichus coffea+TX,
Phytoseiulus macropilus+TX, Phytoseiulus persimilis
(Spidex.RTM.+TX, Phytoline p.RTM.)+TX, Podisus maculiventris
(Podisus.RTM.)+TX, Pseudacteon curvatus+TX, Pseudacteon obtusus+TX,
Pseudacteon tricuspis+TX, Pseudaphycus maculipennis+TX,
Pseudleptomastix mexicana+TX, Psyllaephagus pilosus+TX, Psyttalia
concolor (complex)+TX, Quadrastichus spp.+TX, Rhyzobius
lophanthae+TX, Rodolia cardinalis+TX, Rumina decollate+TX,
Semielacher petiolatus+TX, Sitobion avenae (Ervibank.RTM.)+TX,
Steinernema carpocapsae (Nematac C.RTM.+TX, Millenium.RTM.+TX,
BioNem C.RTM.+TX, NemAttack.RTM.+TX, Nemastar.RTM.+TX,
Capsanem.RTM.)+TX, Steinernema feltiae (NemaShield.RTM.+TX, Nemasys
F.RTM.+TX, BioNem F.RTM.+TX, Steinernema-System.RTM.+TX,
NemAttack.RTM.+TX, Nemaplus.RTM.+TX, Exhibitline sf.RTM.+TX,
Scia-rid.RTM.+TX, Entonem.RTM.)+TX, Steinernema kraussei (Nemasys
L.RTM.+TX, BioNem L.RTM.+TX, Exhibitline srb.RTM.)+TX, Steinernema
riobrave (BioVector.RTM.+TX, BioVektor.RTM.)+TX, Steinernema
scapterisci (Nematac S.RTM.)+TX, Steinernema spp.+TX,
Steinernematid spp. (Guardian Nematodes.RTM.)+TX, Stethorus
punctillum (Stethorus.RTM.)+TX, Tamarixia radiate+TX, Tetrastichus
setifer+TX, Thripobius semiluteus+TX, Torymus sinensis+TX,
Trichogramma brassicae (Tricholine b.RTM.)+TX, Trichogramma
brassicae (Tricho-Strip.RTM.)+TX, Trichogramma evanescens+TX,
Trichogramma minutum+TX, Trichogramma ostriniae+TX, Trichogramma
platneri+TX, Trichogramma pretiosum+TX, Xanthopimpla stemmator;
and
other biologicals including: abscisic acid+TX, bioSea.RTM.+TX,
Chondrostereum purpureum (Chontrol Paste.RTM.)+TX, Colletotrichum
gloeosporioides (Collego.RTM.)+TX, Copper Octanoate
(Cueva.RTM.)+TX, Delta traps (Trapline d.RTM.)+TX, Erwinia
amylovora (Harpin) (ProAct.RTM.+TX, Ni-HIBIT Gold CST.RTM.)+TX,
Ferri-phosphate (Ferramol.RTM.)+TX, Funnel traps (Trapline
y.RTM.)+TX, Gallex.RTM.+TX, Grower's Secret.RTM.+TX,
Homo-brassonolide+TX, Iron Phosphate (Lilly Miller Worry Free
Ferramol Slug & Snail Bait.RTM.)+TX, MCP hail trap (Trapline
f.RTM.)+TX, Microctonus hyperodae+TX, Mycoleptodiscus terrestris
(Des-X.RTM.)+TX, BioGain.RTM.+TX, Aminomite.RTM.+TX, Zenox.RTM.+TX,
Pheromone trap (Thripline ams.RTM.)+TX, potassium bicarbonate
(MilStop.RTM.)+TX, potassium salts of fatty acids (Sanova.RTM.)+TX,
potassium silicate solution (Sil-Matrix.RTM.)+TX, potassium
iodide+potassiumthiocyanate (Enzicur.RTM.)+TX, SuffOil-X.RTM.+TX,
Spider venom+TX, Nosema locustae (Semaspore Organic Grasshopper
Control.RTM.)+TX, Sticky traps (Trapline YF.RTM.+TX, Rebell
Amarillo.RTM.)+TX and Traps (Takitrapline y+b.RTM.)+TX.
The references in brackets behind the active ingredients, e.g.
[3878-19-1] refer to the Chemical Abstracts Registry number. The
above described mixing partners are known. Where the active
ingredients are included in "The Pesticide Manual" [The Pesticide
Manual--A World Compendium; Thirteenth Edition; Editor: C. D. S.
TomLin; The British Crop Protection Council], they are described
therein under the entry number given in round brackets hereinabove
for the particular compound; for example, the compound "abamectin"
is described under entry number (1). Where "[CCN]" is added
hereinabove to the particular compound, the compound in question is
included in the "Compendium of Pesticide Common Names", which is
accessible on the internet [A. Wood; Compendium of Pesticide Common
Names, Copyright .COPYRGT. 1995-2004]; for example, the compound
"acetoprole" is described under the internet address
http://www.alanwood.net/pesticides/acetoprole.html.
Most of the active ingredients described above are referred to
hereinabove by a so-called "common name", the relevant "ISO common
name" or another "common name" being used in individual cases. If
the designation is not a "common name", the nature of the
designation used instead is given in round brackets for the
particular compound; in that case, the IUPAC name, the
IUPAC/Chemical Abstracts name, a "chemical name", a "traditional
name", a "compound name" or a "develoment code" is used or, if
neither one of those designations nor a "common name" is used, an
"alternative name" is employed. "CAS Reg. No" means the Chemical
Abstracts Registry Number.
The active ingredient mixture of the compounds of formula I
selected from Table 1 to 10 with active ingredients described above
comprises a compound selected from Table 1 to 10 and an active
ingredient as described above preferably in a mixing ratio of from
100:1 to 1:6000, especially from 50:1 to 1:50, more especially in a
ratio of from 20:1 to 1:20, even more especially from 10:1 to 1:10,
very especially from 5:1 and 1:5, special preference being given to
a ratio of from 2:1 to 1:2, and a ratio of from 4:1 to 2:1 being
likewise preferred, above all in a ratio of 1:1, or 5:1, or 5:2, or
5:3, or 5:4, or 4:1, or 4:2, or 4:3, or 3:1, or 3:2, or 2:1, or
1:5, or 2:5, or 3:5, or 4:5, or 1:4, or 2:4, or 3:4, or 1:3, or
2:3, or 1:2, or 1:600, or 1:300, or 1:150, or 1:35, or 2:35, or
4:35, or 1:75, or 2:75, or 4:75, or 1:6000, or 1:3000, or 1:1500,
or 1:350, or 2:350, or 4:350, or 1:750, or 2:750, or 4:750. Those
mixing ratios are by weight.
The mixtures as described above can be used in a method for
controlling pests, which comprises applying a composition
comprising a mixture as described above to the pests or their
environment, with the exception of a method for treatment of the
human or animal body by surgery or therapy and diagnostic methods
practised on the human or animal body.
The mixtures comprising a compound of formula I selected from Table
1 to 10 and one or more active ingredients as described above can
be applied, for example, in a single "ready-mix" form, in a
combined spray mixture composed from separate formulations of the
single active ingredient components, such as a "tank-mix", and in a
combined use of the single active ingredients when applied in a
sequential manner, i.e. one after the other with a reasonably short
period, such as a few hours or days. The order of applying the
compounds of formula I selected from Table 1 to 10 and the active
ingredients as described above is not essential for working the
present invention.
The compositions according to the invention can also comprise
further solid or liquid auxiliaries, such as stabilizers, for
example unepoxidized or epoxidized vegetable oils (for example
epoxidized coconut oil, rapeseed oil or soya oil), antifoams, for
example silicone oil, preservatives, viscosity regulators, binders
and/or tackifiers, fertilizers or other active ingredients for
achieving specific effects, for example bactericides, fungicides,
nematocides, plant activators, molluscicides or herbicides.
The compositions according to the invention are prepared in a
manner known per se, in the absence of auxiliaries for example by
grinding, screening and/or compressing a solid active ingredient
and in the presence of at least one auxiliary for example by
intimately mixing and/or grinding the active ingredient with the
auxiliary (auxiliaries). These processes for the preparation of the
compositions and the use of the compounds I for the preparation of
these compositions are also a subject of the invention.
The application methods for the compositions, that is the methods
of controlling pests of the abovementioned type, such as spraying,
atomizing, dusting, brushing on, dressing, scattering or
pouring--which are to be selected to suit the intended aims of the
prevailing circumstances--and the use of the compositions for
controlling pests of the abovementioned type are other subjects of
the invention. Typical rates of concentration are between 0.1 and
1000 ppm, preferably between 0.1 and 500 ppm, of active ingredient.
The rate of application per hectare is generally 1 to 2000 g of
active ingredient per hectare, in particular 10 to 1000 g/ha,
preferably 10 to 600 g/ha.
A preferred method of application in the field of crop protection
is application to the foliage of the plants (foliar application),
it being possible to select frequency and rate of application to
match the danger of infestation with the pest in question.
Alternatively, the active ingredient can reach the plants via the
root system (systemic action), by drenching the locus of the plants
with a liquid composition or by incorporating the active ingredient
in solid form into the locus of the plants, for example into the
soil, for example in the form of granules (soil application). In
the case of paddy rice crops, such granules can be metered into the
flooded paddy-field.
The compounds of the invention and compositions thereof are also be
suitable for the protection of plant propagation material, for
example seeds, such as fruit, tubers or kernels, or nursery plants,
against pests of the abovementioned type. The propagation material
can be treated with the compound prior to planting, for example
seed can be treated prior to sowing. Alternatively, the compound
can be applied to seed kernels (coating), either by soaking the
kernels in a liquid composition or by applying a layer of a solid
composition. It is also possible to apply the compositions when the
propagation material is planted to the site of application, for
example into the seed furrow during drilling. These treatment
methods for plant propagation material and the plant propagation
material thus treated are further subjects of the invention.
Typical treatment rates would depend on the plant and pest/fungi to
be controlled and are generally between 1 to 200 grams per 100 kg
of seeds, preferably between 5 to 150 grams per 100 kg of seeds,
such as between 10 to 100 grams per 100 kg of seeds.
The term seed embraces seeds and plant propagules of all kinds
including but not limited to true seeds, seed pieces, suckers,
corns, bulbs, fruit, tubers, grains, rhizomes, cuttings, cut shoots
and the like and means in a preferred embodiment true seeds.
The present invention also comprises seeds coated or treated with
or containing a compound of formula I. The term "coated or treated
with and/or containing" generally signifies that the active
ingredient is for the most part on the surface of the seed at the
time of application, although a greater or lesser part of the
ingredient may penetrate into the seed material, depending on the
method of application. When the said seed product is (re)planted,
it may absorb the active ingredient. In an embodiment, the present
invention makes available a plant propagation material adhered
thereto with a compound of formula I. Further, it is hereby made
available, a composition comprising a plant propagation material
treated with a compound of formula I.
Seed treatment comprises all suitable seed treatment techniques
known in the art, such as seed dressing, seed coating, seed
dusting, seed soaking and seed pelleting. The seed treatment
application of the compound formula I can be carried out by any
known methods, such as spraying or by dusting the seeds before
sowing or during the sowing/planting of the seeds.
BIOLOGICAL EXAMPLES
Example B1: Activity Against Bemisia tabaci (Cotton White Fly):
Feeding/Contact Activity
Cotton leaf discs were placed on agar in 24-well microtiter plates
and sprayed with aqueous test solutions prepared from 10,000 ppm
DMSO stock solutions. After drying the leaf discs were infested
with adult white flies. The samples were checked for mortality 6
days after incubation.
The following compounds resulted in at least 80% mortality at an
application rate of 200 ppm:
A8, A9, A27, A28, A29, A31, A32, A33, A45, A47, A49, A50, A58 and
A59.
Example B2: Activity Against Diabrotica balteata (Corn Root
Worm)
Maize sprouts placed onto an agar layer in 24-well microtiter
plates were treated with aqueous test solutions prepared from
10,000 ppm DMSO stock solutions by spraying. After drying, the
plates were infested with L2 larvae (6 to 10 per well). The samples
were assessed for mortality and growth inhibition in comparison to
untreated samples 4 days after infestation.
The following compounds gave an effect of at least 80% in at least
one of the two categories (mortality or growth inhibition) at an
application rate of 200 ppm:
A1, A2, A3, A4, A5, A6, A8, A9, A11, A19, A20, A21, A22, A23, A24,
A25, A28, A29, A30, A31, A32, A33, A34, A35, A36, A37, A39, A40,
A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52, A58 and
A59.
Example B3: Activity Against Euschistus heros (Neotropical Brown
Stink Bug)
Soybean leaves on agar in 24-well microtiter plates were sprayed
with aqueous test solutions prepared from 10,000 ppm DMSO stock
solutions. After drying the leaves were infested with N2 nymphs.
The samples were assessed for mortality and growth inhibition in
comparison to untreated samples 5 days after infestation.
The following compounds gave an effect of at least 80% in at least
one of the two categories (mortality or growth inhibition) at an
application rate of 200 ppm:
A1, A2, A3, A6, A8, A9, A11, A12, A14, A15, A17, A19, A21, A22,
A23, A24, A25, A26, A27, A28, A29, A30, A31, A32, A33, A34, A36,
A37, A40, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52,
A58 and A59.
Example B4: Activity Against Frankliniella occidentalis (Western
Flower Thrips): Feeding/Contact Activity
Sunflower leaf discs were placed on agar in 24-well microtiter
plates and sprayed with aqueous test solutions prepared from 10,000
DMSO stock solutions. After drying the leaf discs were infested
with a Frankliniella population of mixed ages. The samples were
assessed for mortality 7 days after infestation.
The following compounds resulted in at least 80% mortality at an
application rate of 200 ppm:
A9, A29, A31, A33, A37 and A51.
Example B5: Activity Against Myzus persicae (Green Peach Aphid):
Feeding/Contact Activity
Sunflower leaf discs were placed onto agar in a 24-well microtiter
plate and sprayed with aqueous test solutions prepared from 10,000
ppm DMSO stock solutions. After drying, the leaf discs were
infested with an aphid population of mixed ages. The samples were
assessed for mortality 6 days after infestation.
The following compounds resulted in at least 80% mortality at an
application rate of 200 ppm:
A3, A5, A6, A8, A9, A11, A12, A14, A15, A19, A21, A22, A23, A24,
A27, A28, A29, A31, A32, A33, A35, A36, A37, A40, A42, A43, A45,
A47, A49, A50, A51, A58 and A59.
Example B6: Activity Against Myzus persicae (Green Peach Aphid).
Systemic Activity
Roots of pea seedlings infested with an aphid population of mixed
ages were placed directly into aqueous test solutions prepared from
10,000 DMSO stock solutions. The samples were assessed for
mortality 6 days after placing seedlings into test solutions.
The following compounds resulted in at least 80% mortality at a
test rate of 24 ppm:
A8, A9, A11, A12, A15, A19, A20, A22, A27, A32, A33, A34, A35, A36,
A37 and A59.
Example B7: Activity Against Myzus persicae (Green Peach Aphid).
Intrinsic Activity
Test compounds prepared from 10,000 ppm DMSO stock solutions were
applied by pipette into 24-well microtiter plates and mixed with
sucrose solution. The plates were closed with a stretched Parafilm.
A plastic stencil with 24 holes was placed onto the plate and
infested pea seedlings were placed directly on the Parafilm. The
infested plate was closed with a gel blotting paper and another
plastic stencil and then turned upside down. The samples were
assessed for mortality 5 days after infestation.
The following compounds resulted in at least 80% mortality at a
test rate of 12 ppm:
A3, A21, A22, A23, A24 and A58.
Example B8: Activity Against Plutella xylostella (Diamond Back
Moth)
24-well microtiter plates with artificial diet were treated with
aqueous test solutions prepared from 10,000 ppm DMSO stock
solutions by pipetting. After drying, the plates were infested with
L2 larvae (10 to 15 per well). The samples were assessed for
mortality and growth inhibition in comparison to untreated samples
5 days after infestation.
The following compounds gave an effect of at least 80% in at least
one of the two categories (mortality or growth inhibition) at an
application rate of 200 ppm:
A3, A4, A5, A6, A8, A9, A12, A15, A16, A21, A22, A23, A24, A28,
A29, A30, A31, A32, A33, A36, A37, A39, A40, A41, A42, A43, A44,
A45, A46, A47, A48, A49, A50, A51, A52, A58 and A59.
Example B9: Activity Against Spodoptera littoralis (Egyptian Cotton
Leaf Worm)
Cotton leaf discs were placed onto agar in 24-well microtiter
plates and sprayed with aqueous test solutions prepared from 10,000
ppm DMSO stock solutions. After drying the leaf discs were infested
with five L1 larvae. The samples were assessed for mortality,
anti-feeding effect, and growth inhibition in comparison to
untreated samples 3 days after infestation. Control of Spodoptera
littoralis by a test sample is given when at least one of the
categories mortality, anti-feedant effect, and growth inhibition is
higher than the untreated sample.
The following compounds resulted in at least 80% control at an
application rate of 200 ppm:
A3, A5, A6, A7, A9, A19, A21, A22, A24, A28, A29, A31, A32, A33,
A37, A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51,
A52, A58 and A59.
Example B10: Activity Against Spodoptera littoralis (Egyptian
Cotton Leaf Worm)
Test compounds were applied by pipette from 10,000 ppm DMSO stock
solutions into 24-well plates and mixed with agar. Lettuce seeds
were placed onto the agar and the multi well plate was closed by
another plate which contained also agar. After 7 days the compound
was absorbed by the roots and the lettuce grew into the lid plate.
The lettuce leaves were then cut off into the lid plate. Spodoptera
eggs were pipetted through a plastic stencil onto a humid gel
blotting paper and the lid plate was closed with it. The samples
were assessed for mortality, anti-feedant effect and growth
inhibition in comparison to untreated samples 6 days after
infestation.
The following compounds gave an effect of at least 80% in at least
one of the three categories (mortality, anti-feeding, or growth
inhibition) at a test rate of 12.5 ppm:
A6, A9, A19, A22, A24, A29, A31, A32, A40, A42, A43, A45, A47, A49,
A50 and A59.
Example B11: Activity Against Tetranychus urticae (Two-Spotted
Spider Mite): Feeding/Contact Activity
Bean leaf discs on agar in 24-well microtiter plates were sprayed
with aqueous test solutions prepared from 10,000 ppm DMSO stock
solutions. After drying the leaf discs were infested with a mite
population of mixed ages. The samples were assessed for mortality
on mixed population (mobile stages) 8 days after infestation.
The following compounds resulted in at least 80% mortality at an
application rate of 200 ppm:
A4, A5, A6, A7, A24, A43 and A45.
Example B12: Activity Against Thrips tabaci (Onion Thrips)
Feeding/Contact Activity
Sunflower leaf discs were placed on agar in 24-well microtiter
plates and sprayed with aqueous test solutions prepared from 10,000
ppm DMSO stock solutions. After drying the leaf discs were infested
with a thrips population of mixed ages. The samples were assessed
for mortality 6 days after infestation.
The following compounds resulted in at least 80% mortality at an
application rate of 200 ppm: A9, A29, A32, A51 and A59.
Example B13: Activity Against Aedes aegypti (Yellow Fever
Mosquito)
Test solutions, at an application rate of 200 ppm in ethanol, were
applied to 12 well tissue culture plates. Once the deposits were
dry, five, two to five day old adult female Aedes aegypti were
added to each well, and sustained with a 10% sucrose solution in a
cotton wool plug. Assessment of knockdown was made one hour after
introduction, and mortality was assessed at 24 and 48 hours after
introduction.
The following compounds gave at least 80% control of Aedes aegypti
after 48 h and/or 24 h:
A6, A8, A9, A22, A24, A28, A29, A31, A32, A39, A40, A41, A42, A45,
A46, A47, A49, A51 and A52.
Example B14: Activity Against Anopheles stephensi (Indian Malaria
Mosquito)
Test solutions, at an application rate of 200 ppm in ethanol, were
applied to 12 well tissue culture plates. Once the deposits were
dry, five, two to five day old adult female Anopheles stephensi
were added to each well, and sustained with a 10% sucrose solution
in a cotton wool plug. Assessment of knockdown was made one hour
after introduction, and mortality was assessed at 24 and 48 hours
after introduction.
The following compounds gave at least 80% control of Anopheles
stephensi after 48 h and/or 24 h:
A6, A9, A22, A24, A40, A45, A46, A47, A49, A51 and A52.
* * * * *
References